Sometime between Janis leaving and the events of the film, Regina dated and broke up with Aaron Samuels and she became best friends with Gretchen Wieners and Karen Smith, with the group becoming known as the Plastics.

She manipulates the people around her into giving her exactly what she wants, including persuading her parents to switch bedrooms or breaking up couples.

On Cady’s second day, Regina notices her being harassed by Gretchen Wieners' boyfriend Jason and invites her to sit with The Plastics.

Her tactics work as Cady accepts the invite to join The Plastics and thinks of Regina as a sweet girl.

When Regina arrives at school wearing sweatpants on a Monday, something The Plastics prohibit, Gretchen and Karen tell her she can't sit with them.

Regina tries to gain their sympathy by saying that her weight gain means sweatpants are all that can fit her, however, Gretchen and Karen do not care due to Regina doing the same to them in the past and bubbling tensions between them since Cady's revenge plot began.

Regina adds herself to the Burn Book, meaning only Cady, Gretchen, and Karen are not mentioned in it.

Due to the chaos, a workshop begins in the gymnasium for all the girls, in which they have to apologize to people they have hurt with their behaviour.

Once her spine heals the following year, Regina is advised by her physiotherapist to channel her anger through sports, which she does as she joins the lacrosse team.

[4] Taylor Louderman was nominated for the Tony Award for Best Actress in a Musical for her performance as Regina.