After being rattled by a battle among the boys, a pregnant Lois ponders the consequences of raising another brawling kid. So she fantasizes that her unruly sons have morphed into well-behaved young daughters. Malcolm becomes Mallory, Reese is transformed into Renee and Dewey turns into Daisy.
Malcolm is a regular high school kid trying to navigate his way through life despite the various obstacles thrown in his way a complete misunderstanding of girls, the constant burden of masterminding plans to get himself and his brothers into or out of trouble, and a miserable job at the Lucky Aide not to mention a severe case of teen angst.
Although Malcolm has a genius IQ, he can't seem to make sense of the opposite sex, much less his embarrassing family. Lois is the outspoken, opinionated mom, who still manages to rule the roost even though her boys are growing wise to her crafty ways. Hal, a dad who is just a bumbling, big kid at heart, often finds himself creating more chaos than his five boys combined.