The game takes place in 22th century. Scientists developed a new technique that allowed them to merge the DNA of humans and animals, producing powerful creatures known as "gears". The characters of the game participate in a tournament, the winner of which would face a gear who went out of control and is threatening to lead a gear rebellion against the humans. The game allows you to play as familiar characters from Guilty Gear series, such as the main hero Sol Badguy, who has a certain connection to the gears, and his rival, the leader of the Holy Knights named Ky Kiske. It also introduces a new character, the nurse Fanny, who fights with a syringe and has a mysterious connection to the genius surgeon, and later serial murderer, Dr. Baldhead.

Guilty Gear Petit is a 2D fighting game. The story mode lets you pick a character and take him/her through a series of fights, while in time attack mode you can choose your opponents freely. The graphics are done in "super-deformed" style. The game retains key ingredients of Guilty Gear gameplay, such as building tension in order to execute powerful attacks, combo moves, etc.