NOTE: This spoiler was submitted by Jeremy

The film opens with Janis ‘Imi’ike (Auli’i Cravalho) and Damian Hubbard (Jaquel Spivey) in a garage as they introduce the story (“Cautionary Tale”), featuring romance, drama, betrayal, and someone getting hit by a bus.

Sixteen-year-old Cady Heron (Angourie Rice) has been homeschooled in Kenya her whole life, but is now getting ready to go back to the United States with her mother (Jenna Fischer) to be enrolled in public school (“What Ifs”). Cady begins attending North Shore High School. She meets teachers like Ms. Norbury (Tina Fey), Coach Carr (Jon Hamm), and Madame Park (Ashley Park), but has trouble befriending other students.

During lunch, Janis and Damian invite Cady to join them when they find her eating alone in the bathroom. They bring her back to the cafeteria where they show her the different types of cliques she can join, right before Cady spots The Plastics, the most popular and nastiest girls in school. Janis and Damian talk to Cady about Gretchen Wieners (Bebe Wood), who is rich but emotionally fragile, and Karen Shetty (Avantika), who is pretty but incredibly dumb. They are led by the resident queen bee, Regina George (ReneĆ© Rapp), who strikes fear into the hearts of the other students (“Meet The Plastics”). Cady catches Regina’s eye and is invited to go over to their table. Another student, Jason Weems (John El-Jor) comes over to make a crude comment to Cady, and Regina proceeds to humiliate Jason in front of the whole cafeteria. Regina invites Cady to eat lunch with her and Gretchen and Karen for the rest of the week, which Janis and Damian see as an opportunity for Cady to get dirt on the Plastics.

In her calculus class, Cady develops a crush on handsome senior Aaron Samuels (Christopher Briney), and starts pretending to dumb herself down in order to spend time with him (“Stupid With Love”). Meanwhile, Janis and Damian are annoyed at Cady’s lack of info on The Plastics. They warn her not to fall for any of Regina’s tricks, as she has a way of controlling the other students around her (“Apex Predator”).

Cady joins the girls at Regina’s house, where she meets Regina’s mother (Busy Phillips). In Regina’s room, Cady tells Gretchen and Karen that she likes Aaron, but the girls warn her not to mention that to Regina because Aaron is her ex-boyfriend. Regina’s mom then pulls out a “Burn Book” that the Plastics created to write mean things about other girls in their grade. Janis has “psycho lez” written next to her picture while Damian gets “too gay to function” on there after Cady brought it up (because Janis introduced him that way). The girls tell Cady and Janis and Regina used to be friends until Janis apparently got obsessed and set Regina’s backpack on fire. Meanwhile, Gretchen is shown to be too dependent on Regina (“What’s Wrong With Me?”).

Aaron later invites Cady to a Halloween party. Gretchen and Karen get ready by trying to find the hottest costume (“Sexy”) while Cady dresses like a grotesque zombie bride. Gretchen lets it slip to Regina that Cady likes Aaron, so Regina pretends to go talk to him for Cady. In reality, she uses one of her manipulation tactics (“Someone Gets Hurt”) before pulling Aaron in for a kiss. Cady witnesses this and feels betrayed, going back to Janis and Damian to declare that she now hates Regina as much as they do. When Cady brings up the backpack story, Damian clarifies the story as that Regina kissed Janis during a game of Spin The Bottle and later started a rumor that Janis had an obsessive crush on her and even used a plush doll to make fun of her. Janis set the plush doll on fire, which set Regina’s backpack on fire, and got Janis kicked out of school for the rest of the year. Cady then goes along with Janis and Damian’s plan to ruin Regina’s life.

The trio starts their revenge scheme (“Revenge Party”) by sabotaging Regina when she is getting awarded homecoming queen. Janis turns on the sprinklers to ruin her makeup, but the running mascara look catches on, and all the other girls (and Madame Park) start copying the look. Cady then starts giving Regina Kalteen Bars to supposedly make her lose weight, even though they make people gain weight quickly. Janis and Damian also have Cady give Regina face cream that is actually just lard.

Janis and Damian then have Cady start to get Gretchen and Karen to turn against Regina. Around the holidays, they make it so that it looks like Regina sent Cady a candy cane gram and none for Gretchen, causing her insecurity to boil over and spill some of Regina’s secrets to Cady, which she records. One of these secrets is that Regina is cheating on Aaron with Shame Oman (Brian Altemus), which Cady tells him about, and he catches Regina and Shane making out in the janitor’s closet, leading Aaron to break up with her.

Cady later joins The Plastics for their annual talent show Christmas performance. (“Rockin’ Around The Pole”), which everyone in the school is sick of. Damian sings the “iCarly” theme in French while Mathlete Kevin Ganatra (Mahi Alam) does a crude rap. After Regina insults both Gretchen and Karen (Karen’s outfit and Gretchen’s repeated use of “fetch” as slang), they do their dance, which takes a disastrous turn when Regina, Gretchen, and Karen all take a tumble onstage while Cady continues to dance. The incident goes viral on TikTok, with people mocking Regina and beginning to praise Cady. During lunch, Gretchen and Karen no longer allow Regina to sit with them since she is now wearing sweatpants due to her weight gain.

Janis later invites Cady to her art show, but Cady lies and says she is going somewhere with her mom. Cady then lies to her mom to get out of plans with her so that she can have the house to herself and throw a party so she can invite Aaron. Things go disastrous when the other students trash her house. Cady also gets very drunk and tries to talk to Aaron but just ends up telling him how she pretended to be dumb to talk to him. He starts to get put off by her behavior and leaves. When Cady follows him out, she finds Janis and Damian at her house, both angry at Cady for lying to them and being just as bad as Regina. Cady then hits back that Janis is obsessed with her, which is the final straw and causes Janis and Damian to stop being friends with her (“Someone Gets Hurt (Reprise)”). Janis leaves Cady with her winning art piece, a drawing of the three of them.

Regina later finds out from her mom that the Kalteen Bars are making her gain weight. In a fit of rage, Regina then brings her Burn Book to school (“World Burn”) and plants it for everyone to find. The pages and contents in the book soon go viral, leading to a brawl across the high school between all of the girls. Principal Duvall (Tim Meadows) breaks it up and has all the girls (and Damian) gather in the auditorium.

Ms. Norbury, who was accused in the book of being a drug dealer, has all the girls get together and deliver apologies to each other in a trust fall exercise. After several comments, including the one girl who “doesn’t even go here”, Janis gets up and confesses to Regina her and Cady’s whole revenge scheme against her and how they ruined her life. Janis runs around the school proud of herself (“I’d Rather Be Me”) while Cady and Regina argue after the big revelation, leading to a bus plowing into Regina.

Rumors go around the school that Cady pushed Regina in front of the bus, but she is recovering with a neck and back brace. After realizing that the lives of many girls and Ms. Norbury were affected by the Burn Book, Cady chooses to take full responsibility and gets suspended for three weeks. Upon her return, her grades begin to improve, and Ms. Norbury offers her a way to get extra credit.

Cady joins the Mathletes for their state championship. After a few rounds, the moderator (Lindsay Lohan in a cameo) brings Cady and the other team’s female opponent for the tie-breaking question. Cady tries to be friendly with the other girl, who is rude to her, before the other girl announces an incorrect answer. Cady reflects on what she has gone through (“Stupid With Love (Reprise)”) before giving the correct answer and winning the tournament. She then heads to the school for the Spring Fling dance.

In the bathroom, Cady finds Regina and makes peace with her, mostly because Regina is high on painkillers. Before the winners of the Spring Fling king and queen are announced, Cady tries to find Janis and Damian to reconcile with them. Shane is announced as king while Cady is announced as queen. She gives a speech to everyone about how they are all special (“I See Stars”) and shares pieces of her tiara with everyone, including The Plastics. Janis and Damian forgive Cady, and she goes to dance with Aaron, where they share their first kiss.

Janis and Damian conclude the story by delivering the moral that everyone in school is just trying to live their lives, and for everyone to “stay off each other’s dicks”.

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Much like the original film, Cady starts public school after being homeschooled in Kenya her whole life. She makes friends with outcasts Janis and Damian before befriending the popular and nasty Plastics - Regina, Gretchen, and Karen. The girls let Cady into their clique, which gives Janis and Damian a plan to have Cady get dirt on Regina as revenge for Regina outing Janis as a lesbian when they were younger.

After catching Regina kissing her crush, Aaron, Cady joins along the revenge scheme and finds ways to ruin Regina's life, by giving her bars that make her gain weight instead of helping her lose it as Cady had said, along with getting Aaron to break up with Regina after seeing that she cheats on him. Cady starts to become as popular as Regina but also starts to become a mean girl herself, which causes a rift between her and Janis and Damian.

Regina catches on to the scheme and plants her Burn Book full of nasty comments on every girl in the school to instigate a brawl between everyone. After their teacher Ms. Norbury (who also had words written about her) makes all the girls apologize, Janis confesses to the whole scheme, which leads to Cady and Regina arguing, and Regina gets hit by a bus.

After realizing how she has negatively affected other peoples lives, Cady takes responsibility for the Burn Book and gets suspended. When she returns, she helps the Mathletes win the state championships before going to the Spring Fling dance. She wins Spring Fling Queen and uses her chance to give a speech to the whole school, saying that they are all special before making peace with Regina, reconciling with Janis and Damian, and dancing and kissing with Aaron.