Like with previous installments in the series, Super Bust-A-Move 2 has the player match coloured bubbles to clear the screen of bubbles. To do so, the player launches a bubble from the bottom of the screen towards the top and tries to attach it to bubbles of the same colour. Once three or more bubbles match, they are removed from the playing field. Removing extra bubbles of unrelated colours gives extra points. After destroying a certain number of bubbles, a new row appears at the top of the screen. Once the bubbles reach a certain line at the bottom part of the screen, the game is over.

There's a variety of special bubbles available, some of them acting as bombs for example, while others randomly colour the bubbles they hit. The game also contains several different play modes: story mode (with several different characters to choose from, some of them hidden), duel mode and single player puzzle. In addition, there's an edit mode that lets the player create custom puzzles to let their friends play.