Otome wa Boku ni Koishiteru revolves around the main protagonist Mizuho Miyanokouji, a male high school student. After Mizuho's grandfather dies, his will is reviewed, which explains his desire to have his grandson transfer to Seio Girls' Academy, the same one his own mother attended and his ancestors founded. Abiding by the will, Mizuho cross-dresses to attend the school. The headmistress, the deputy head teacher (visual novel only), Mizuho's homeroom teacher Hisako Kajiura and Mariya Mikado initially know his secret; Sion Jujo and Ichiko Takashima also eventually find this out. Mizuho is very popular among the other students, who often talk about how pretty, nice, and athletic Mizuho is. This rampant popularity escalates to him even being nominated against his will to join in on the Elder election. By these terms, the current student council president, Takako Itsukushima, runs against Mizuho.
When Takako tells Kana to remove the ribbon in her hair during school, Mizuho, Mariya and Shion challenge the student council president's opinion in front of the entire school.
Yukari starts to lose confidence in herself when it comes to her activity in the Track and Field club while everyone else around her are working so hard. What will it take for her to regain it?
After witnessing how mature Mizuho has grown recently, Mariya is unsure on how to act towards him and starts to avoid him. Mariya also starts to take notice of her feelings towards Mizuho.
The school festival has finally begun and all the students are working hard at their respective exhibits. Now's the moment that everyone's been waiting for: the play Romeo and Juliet starring Mizuho and Takako.
Mariya has come down with a cold while still trying to battle with her feelings for Mizuho. After she recovers, what will happen when they go out on a date together?
After learning that Mizuho is in fact male, Takako starts to avoid him at school. The rest of the students notice the change in her, and in Mizuho's personality. However, the dance party is still coming up and Mizuho has resigned to fulfill his Elder duties and be there. Takako has some misgivings about going, but after a talk by Mariya, she attends and is even able to share the last dance with Mizuho. In the credits, the main characters are shown enjoying themselves over the rest of the remaining school year.
Continuing from last episode, Mizuho introduces Ichiko to the dorm girls. Mizuho learns of Ichiko's past, that Ichiko's elder friend is his own mother. After Ichiko had cleared her conscience, Mizuho thought that Ichiko had passed on only to later discover she is back at the dorm and is there to stay.
As the summer vacation draws closer, the students begin swimming for physical education, though Mizuho has to fake being on a menstrual cycle to get out of it. When Takako notices him skipping out on swimming, she has the false pretense that Mizuho can't swim though is told yet another lie that Mizuho is afraid of water. Mariya and Takako get in a fight afterwards and end up in a swimming contest as many other students watch and cheer on.
Mizuho finds out he is in the same world history class with Takako, where they talk and she says that she won't agree to her becoming elder, not knowing that he's a boy. Mizuho is elected elder and Shion collapses after defending the election, making Mizuho rush her to the infirmary.
After the girls (and Mizuho) did a "scary stories night", the story of the ghost that has been living in one of the dorm's rooms - Mizuho's - is revealed. Takashima Ichiko is awakened and introduced.
Shion Jujo is introduced and befriends Mizuho. Shion quickly realizes Mizuho is male, but doesn't seem to care. Mizuho learns of the Elder system, where a model student is chosen by students and of Shion's connection with it.
Mizuho, despite being male, is transferred to an all-girls school where he must crossdress in order to attend. Upon arrival, he quickly becomes popular among the other students.