Modeled after Guilty Gear Isuka, its gameplay allows up to four player fights.

It was the first versus fighting game for the Nintendo DS to be released outside Japan.

Guilty Gear: Dust Strikers is also the first Guilty Gear game so far to have mini-games, ranging from the Balance Game where the player must help a chibi Jam balance the falling items with her plate, to Venom's Billiards, which puts the player and opponent in a pool-style game.

The boss of the game's Story and Arcade modes is Gig, an immense insect-like monster with an angel attached to its bottom half.

Guilty Gear Dust Strikers received "mixed or average reviews", according to Metacritic.