The console version of Spider-Man 2 is a third-person action-adventure video game, set in an open world based on New York City and composed of Manhattan, Roosevelt Island, Ellis Island, and Liberty Island. Players take on the role of Spider-Man and complete missions—linear scenarios with set objectives—to progress through the story.

The story is divided into multiple chapters, each with its own set of objectives, such as purchasing upgrades for Spider-Man, or acquiring a certain number of hero points from completing side missions. These side missions are given by random pedestrians across the game's map, and mainly consist of battling criminals, stopping speeding cars by jumping on top of them and punching them, taking injured people to the hospital, or saving construction workers from falling to their deaths. Each chapter includes at least one story mission related to the main plot.

Players are able to web swing, crawl walls, and fight enemies using a variety of combos. They can use Spider-Man's "spider sense" to slow down time and dodge incoming attacks, including gun fire. This version of the game was considered innovative at that time due to its physics-based algorithms that simulate Spider-Man's web swinging in three dimensions, creating a new game mechanic unlike the traditional jumping or flying of previous Spider-Man games. Combat is far more complex, as it involves carefully timing the player's attacks and dodges. After completing the main storyline, a bonus mode inside a warehouse is unlocked, where the player can fight waves of enemies and bosses from the main storyline, as well as an exclusive villain: Calypso.