The player controls Yoshimune, exploring Ikebukuro and interacting with the residents. The player can also interact with objects and the setting, such as winning a prize from a crane game or entering the chat room. As the story progresses, Yoshimune will end up with the Dollars, the Yellow Scarves, or something else, depending on the player's decisions.
Yoshimune Miyoshi is a student from the countryside who transfers to Raira Academy. He befriends classmates Mikado Ryuugamine, Anri Sonohara, and Masaomi Kida. While the gang is hanging out in Ikebukuro, they see Shizuo Heiwajima and Izaya Orihara fighting, and the trio warns Yoshimune about them. They later see the trio's acquaintances Celty Sturluson, the legendary Headless Rider, and Shinra Kishitani, an unlicensed underground doctor. Yoshimune is later involved in a strange incident involving the Dollars, the Yellow Scarves, and the Saika Army.
- Yoshimune Miyoshi - The game's main protagonist. Known as "Yoshi-Yoshi" by his friends, he becomes involved in a strange incident in Ikebukuro. Depending on the gameplay, he'll end up becoming either a darker version of himself or a hero with the same personality.
- Chiaki Igarashi - A freshman from a private girls' high school called Elizabeth Girls' College. She has a bright and frank personality.
- Koji Yatabe - The Yellow Scarves' second-in-command. Though he is first introduced in the game, he also appears in the anime and later in the Durarara!! SH novels.