FBI agent Malcolm Turner goes undercover once more as the robust and witty Big Momma. This time, his stepson Trent Pierce finds himself in mortal danger after witnessing a murder at a music school. To protect him, Malcolm brings Trent along on a mission to a performing arts school for girls. They pose as Big Momma, the school's new housemother, and Charmaine, her great-niece. Malcolm is resourceful and wise in his disguise, cleverly navigating the school's routines and maintaining his cover amid a myriad of challenges, while trying to locate incriminating evidence and keep both himself and Trent safe.

As they dive deeper into their undercover roles, Malcolm gets drawn into the dynamics of the students and staff, balancing his FBI duties with the antics and demands of school life. Meanwhile, Trent looks to further his musical aspirations amidst threats and close encounters, all while maintaining his Charmaine persona. Danger looms as the criminal elements grow suspicious, and maintaining their disguises becomes increasingly difficult. Malcolm and Trent must use their wit, skills, and newfound friendships to stay ahead and foil the criminals, while navigating the complexities of their dual lives.