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Medusa is a supporting antagonist in the 2010 film Percy Jackson and the Olympians: The Lightning Thief. She is one of the three guardians of Persephone's Pearls, along with the Hydra and the Lotus Eaters.
She is portrayed by Uma Thurman, who also portrayed Poison Ivy.
In the past, Medusa was a gorgeous woman with beautiful hair who was courted by many suitors and even dated the god Poseidon. However, the goddess Athena eventually cursed her by transforming her into a Gorgon. Afterwards, she went to live in a garden statuary shop called Aunty Em's Garden Emporium and became the guardian of one of Persephone's Pearls. During the following years, she petrified a large number of people who came to visit her domain, including a satyr named Ferdinand.
One day, a couple stops over Aunty Em's Garden Emporium to ask directions, but Medusa turns the man into stone while the woman escapes her. Later that day, Percy Jackson, the son of Poseidon, Annabeth Chase, the daughter of Athena, and Grover Underwood, the nephew of Ferdinand, arrive at the shop looking for the Pearl and split up to find it faster. Annabeth encounters the woman who asks her for help and they try to leave the place, however they are cornered by Medusa. The Gorgon first petrifies the woman before trying to do the same with Annabeth, but she keeps her eyes closed. However, Medusa hears Percy who is hidden nearby and is using the reflection of his iPod to see her, so she pursues him throughout the place and finally manages to trap him under a statue. After disarming him, she grabs Percy and tries to make him open his eyes with her snake hair, but Annabeth and Grover crash a pickup truck into the statues and a debris hits Medusa, knocking her down. She gets up and notices Percy's iPod on the floor, so she picks it and sees in the reflection Percy attacking her in the back. He manages to behead her with his sword, then he takes the Pearl from her bracelet and Annabeth decides to keep her head.
At night, a cleaning woman sees Medusa's head in the hotel room of Percy, Annabeth and Grover, forcing them to leave.
During the fight against the Hydra, Grover gets the idea to use the head to petrify it.
Some times later, Medusa's head is locked in Sally's bridge. Wanting to drink a beer, Gabe opens it and the head turns him into stone.