Tina Fey always wanted Reneé Rapp to play Regina after seeing her performance in the Broadway musical, but she was nervous that the executives at Paramount would want to cast someone trendier. She was happy to hear that Paramount also wanted Rapp for the role.
Ashley Park appears briefly as the students' French teacher. She originated the role of Gretchen Weiners in Mean Girls on Broadway.
Ms. Norbury (Tina Fey) scolds a student for profanity by saying "Hey! PG-13!" Many of the racier jokes from Fey's original screenplay were cut from the 2004 film in order to secure a PG-13 rating rather than an R.
Throughout the whole film, Principal Duvall is seen wearing a cast as a joke since in the original film, Principal Duvall explains that "My carpal tunnel came back" to cover the fact that Tim Meadows had actually broken his hand just prior to filming.
Tina Fey and Tim Meadows reprised their characters of Ms. Norbury and Mr. Duvall respectively 20 years after the original Lolita malgré moi (2004).
Megan Thee Stallion: As herself, commentating on some of the major events in this film on social media. She also contributed to this film's soundtrack, and collaborated with co-star Reneé Rapp on Reneé Rapp & Megan Thee Stallion: Not My Fault (2024).