Mei no Naisho revolves around the life of the title character Mei Haruna, an effeminate young boy who was raised by his witch mother as a girl, and always thought of himself as female. His mother was the only family he had, so after she died, he transfers to an all-girls high school and comes to reside in the school's dormitory with his talking familiar cat Abel, and his roommate Fuuka Honjou, who is also a member of the public morals committee.

Shortly after arriving at the school, his new friends discover after a magical display in the dormitory community bath that he is actually male, though this comes as quite a shock to him despite him being aware of the physical differences between him and normal girls. Despite him being found out, and after some helpful intervening of the perverted student council president, the principal of the school decides that he can stay at the school.

The next day, Mei comes to school with Fuuka and apologizes for hiding the fact that he was a witch, and informs the others how he is apparently male. The other students quickly accept him as one of their own, and are impressed how he can use magic.