Medusa is a very lonely being due to her inability to communicate with others, and this is because of her uncontrollable power of turning people into stone. Her only companions are her living snake hair and the many statues that decorate her grove which she usually pretends to talk to in order to lessen her loneliness. She is also very self-conscious as shown when Aphrodite and Hades both made her an offer to allow her to get close to Hercules, she preferred Hades' deal since it would make her human as opposed to Aphrodite's deal which would not change her "ugly" appearance.
However, she soon becomes depressed for living a lie and willingly reveals her true form to Hercules. Heartbroken when she's rejected, she goes back to her grove and is guilt-ridden when she accidentally turns Hercules to stone (thanks to Hades) when he'd been coming to apologize.
When Hades prepares to make Medusa permanently human, she willingly passes it up and makes sure the magic restores Hercules, and learns her lesson that real friends accept you for who you are, not for what you pretend to be.
When an unconscious Hercules falls from a waterfall after saving Icarus he washes up near Gorgon Land where he is rescued by Medusa who begins to admire the unconscious boy's face, but after an interruption from Icarus and Pegasus who are looking for him she runs away. Later on after having some one-sided conversations with some statues she finds Hercules' school ID, this causes her to crave a normal life more and more so she beseeches the Olympian Gods to help her, her call is answered by Hades, lord of the dead and Aphrodite, the Goddess of Love. Hades offers her an opportunity to become a human by day in exchange for working for him at night as a monster while Aphrodite offers Medusa special sunglasses that would block her powers, allowing her to interact with the world while still being herself. She ends up taking Hades' offer, thinking nobody could see past her true form. To sweeten the deal, Hades adds the twist that, if someone can accept Medusa for who she truly is, he will turn her human permanently and release her from his service.
Things go well for her until a chaotic trip to the Pita Pit where at sunset, she starts her transformation and ends up causing a gorgon panic throughout Athens.
She soon becomes guilt-ridden for living a lie and willingly reveals herself as a gorgon to Hercules, hoping he'll accept her. But Hercules immediately accuses Medusa of wanting to turn him to stone, hurting her feelings and bringing her to tears.
Hercules tells Icarus what happened, and makes the mistake of referring to Medusa as a freak. Angered, Icarus asks if Hercules is gonna cut off Medusa's head, put it in a purse, if he's gonna get rid of all the freaks. Particularly the "freak" who flew too close to the sun.
Hercules realizes his errors and goes to see Medusa intending to apologize and give her flowers. But when Hades learns that Hercules is the guy Medusa has a crush on, he lied to her that Hercules has come to slay her. Then he makes sure Hercules sees Medusa's eyes, turning him to stone. Medusa is heartbroken and realize he brought her flowers to apologize, when Aphrodite appears, reminding Hades of the better part of Medusa's deal. He prepares to turn her human permanently, but she uses Hercules' shield to turn the magic on him, saving him from his petrified state, much to Hades' fury.
Having learned her lesson, Medusa accepts going on a date with Hercules and asks Aphrodite for the shades, and she proudly gives them to her, enabling Medusa to safely interact with Hercules.
Medusa appears on the show like a dangerous creature, similar to her original description in the Greek mythology. Medusa lives in a cavern near the old Summer Palace of the Enchanted Forest. She gains a notorious reputation as a creature who can turn anyone into stone if the person looks straight into her eyes. One day, she chases two intruders, Snow White and Prince Charming, after they purposely enter into her home. While Prince Charming goads Medusa into coming after him, Snow White hides in wait to cut off her head. Surprisingly, the sword has no effect on Medusa and she entraps Prince Charming, forcing him to meet her gaze, and thus transforming him into a stone statue. Medusa goes after Snow White next, but is tricked into meeting her own reflection and immobilizing herself into stone. From her own downfall, Prince Charming is freed.
- Medusa is based on the mythological gorgon Medusa, however she shares very little similarities to her other than being a mortal gorgon. Another trait is that unlike the original myths it is implied in her debut episode that the gorgons are a mortal race of both males and females rather than being a group of two immortal sisters and one mortal sister. This may imply that the character is just a regular gorgon who was simply named after the original.
- Another difference to note between her and her mythical counterpart is that she seems to have no ill feelings towards the gods, even praying to them for help. Which is odd since it was Medusa being used by Poseidon and Athena's wrath that lead to her being cursed in the first place.
- The gorgon that briefly appears in Hercules, during the "Zero to Hero" musical segment, was designated as "Medusa" in Disney's Hercules Playstation game as the girlfriend of Hades. However, the animated series identifies this gorgon as Stheno and Medusa as a separate character.