Ishigami is the art teacher at Yokai Academy and is the ultimate antagonist of the first season, revealing herself as the driving force behind the Safety Commission. She is the legendary gorgon Medusa with her braided hair standing in for the snakes of a gorgon. Her bite can instantly turn its victim into stone, but she lacks to ability to turn people into stone with a gaze. Ishigami has a desire to turn any attractive female student into stone to add her to collection of living art, but is stopped by Tsukune and Moka, resulting in her immediate sacking from the faculty. Ishigami later returns during the Protection Committee arc, secretly informing them of Tsukune's human nature as well as in an attempt of having her revenge, but immediately leaves the scene after Kuyo's defeat.
In the final chapters of the first series, Ishigami reveals it was she who gave Kyoko, Tsukune's cousin, the Lilith Mirror with the intention of stealing his soul and the added bonus of releasing all the students into their monster forms through the powers of the artifact in order to create an uproar that will destroy the school, stating how death and destruction is the purest form of art. Ishigami is defeated a second time and arrested. She also appears in Rosario + Vampire: Tanabata's Miss Yokai Academy as the final boss of the game.