After Susanna (Winona Ryder), a 17-year-old high school student who wants to be a writer, downs all the pills in a bottle of aspirin with a whole bottle of vodka, her upper-middle-class parents send her to a psychiatrist who diagnoses her as having a borderline personality disorder. Susanna, in a voiceover, says: "Maybe I was really crazy, maybe it was the 60s or just a girl, interrupted." She follows the psychiatrist's orders and checks into Claymoor, a psychiatric hospital in New England.

The shy Susanna falls under the influence of Lisa (Angelina Jolie in an Academy Award-winning performance), a wild anarchistic soul who has been there for eight years. She teaches the newcomer how to "tongue her meds," to toy with Dr. Melvin (Jeffrey Tambor), and to join her and several other girls on late night romps through the facility's administration offices. Susanna also befriends Polly (Elisabeth Moss), a self-inflicted burn victim with a badly scarred face, and Daisy (Brittany Murphy), an incest victim with an addiction to laxatives.

Director James Mangold (Heavy), along with Lisa Loomer and Anna Hamilton Phelan, has adapted Susanna Kaysen's best-selling 1993 book for the screen. The drama makes the point that society still doesn't know how to deal with the multiple yearnings of women who don't want to follow in their mothers' path. In several sessions with Dr. Wick (Vanessa Redgrave), Susanna is brought face-to-face with her promiscuity — an affair with a married professor, a romantic tryst with a hippie (Jared Leto), and a brief fling with a hospital employee. Perhaps the best advice she receives comes from Valerie (Whoopi Goldberg), a sensitive nurse who tells her she's "a lazy, self-indulgent, little girl who's driving herself crazy." In the end, Susanna learns about her self-destructive tendencies and the value of life together in community. She returns to the "normal world" armed with a story to tell.