Medusa is the first and most active main antagonist in Soul Eater. She is the witch who is the mother of Crona and manipulates Crona into collecting every soul they come across. She is the one that told Crona that it was okay to take any soul they wanted. When Crona starts to falter, Medusa plants a hypnotic spell in Crona's mind that makes Crona want to fight and kill. She poses as a teacher and a nurse at Shibusen so she has access to all the students files. While in disguise, she acts like a very supportive person to hide her true nature. She stays at Shibusen to study the students to see which ones can become kishin (demon gods). Medusa is willing to use anyone and everyone to further her plans by any means necessary (even as far as planting snake bombs in her fellow witches bodies so they would cooperate with her). She can use them without dropping her soul protection, which allows her to not be discovered by others. Her personality is similar to Dr. Stein as she sees everyone and everything as an experiment. Her animal theme is snakes due to her magic, clothes, and that she constantly chants "Nake snake cobra cobubra". She has thousands of snakes in her body ready to do her bidding. She engaged in an intense battle with Dr. Stein in the lowest level of the school to allow the awakening of the first kishin. While she initially had the upper hand, her momentary pleasure at Asura's successful resurrection allowed Stein to slice her in half. Making one final attack and claiming to love him, he skewered her through the skull and her body evaporated. However, a snake decorated with Medusa's arrow markings was seen escaping the city through a drainpipe on the outskirts, most likely her transformed. Medusa has now been proven to still be alive, having possessed a cute little girl called Rachel. After getting her hands on the legendary artifact "BREW", leads a group of Shibusen students in an attack against a fellow witch — her older sister Arachne.

Magic: Her magic attacks in the form of snakes and uses the concept of vectors (directions).

* Vector Arrow: Sends arrow headed snakes to pierce the enemy. (follows Medusa's hands)

* Vector Bullet: An arrow appears on the ground that will send anything on it in the direction that Medusa desires; propelling herself towards the enemy to engage in close combat (against Dr. Stein and Crona), propelling an attacker away from her, and quite possibly moving inanimate objects like chairs, tables, etc., turning them into deadly projectiles. Also known as Vector Plate in the anime and some translations.

* Serpent Whip: Medusa extends one of her snakes to strike from afar. Known as Light Serpent in the anime.

* Steam Vector: This attack surrounds Medusa with her Vector Arrows making a spinning tornado like shield. Called Vector Storm in the anime.

* Snake Bomb: Places a snake from her body into someone else; it will only detonate when she gives the signal.

* Vector Boost: A magic that doubles the power drawn in the direction of the arrow.