A human-demon hybrid born to the legendary demon, Sparda, and a human woman. Though he hates demons with every fiber of his being, Dante is a fast-talker with a flippant attitude. Despite being young, he's an exceptionally skilled fighter who expertly wields his father's old longsword, Rebellion, and a pair of handguns named Ebony and Ivory.
He's committed to slaying demons wherever they may appear, but in the meantime he runs a handyman shop. Dante flourishes when hunting down demons.

Dante's twin brother. Vergil is also a human-demon hybrid, but unlike Dante, who chooses to live as a human, Vergil has chosen to embrace his demonic side. He has a steel will and is happy to sacrifice anything and anyone to achieve his goals. He went missing one year ago, but he has suddenly reappeared before Dante with demons in tow. Vergil's thirst for power has led him to activate Temi-Ni-Gru, which will open the gate to the demon world.

A young woman who just happens to hunt demons. She harbours an intense hatred for demons and seeks to exterminate them all by herself. Lady sets out to climb the tower on her own in order to exact revenge on Arkham for the death of her mother. She opposes Dante because of his demonic blood, but the two come to an understanding after their initial fight. "Lady" is just a nickname that Dante gives her, her real name is Mary, given by Arkham.

A man who wishes to become a demon. He sacrifices his own wife in a ritual to that end, but the attempt failed, and Arkham received incomplete demonic powers. His next plan is to become an almighty god. He feigns cooperation with Vergil and heads for the tower in order to break Sparda's seal in the demon world.

A mysterious character who lurks in Temi-Ni-Gru, the tower that connects the human and demon worlds. His confounding words and actions befit his clown-like appearance. Jester is intimately familiar with the tower and frequently shows up to offer Dante guidance. In the end, Jester turns out to be Arkham in disguise.