The plot follows a martial artist protecting his companion and wielding a legendary divine arm called the "God Hand", in order to save the world from demons.

[6] Using the button allows the player, as Gene, to jump up ladders, pick up items, and use special attacks on abnormal enemies.

[6] There are over one hundred moves in the game for the player to choose from including basic jabs and punches to drunken-style and capoeira martial arts.

[7] These moves are limited to a number of "Roulette Orbs" that the player can increase by collecting "Skull Cards" found throughout each stage.

[8][10] When it reaches a set amount, the player can remove the bracelet from Gene's arm to temporarily unleash the God Hand.

Defeating enemies at higher Difficulty Levels earns the player more bonus points at the end of a stage.

[6][11] Also accessible from the map is a casino, which contains a number of minigames, including slots, blackjack, poker, chihuahua racing and a fighting arena.

The game features a number of recurring minor enemies whom Gene meets, including a pair of extremely flamboyant twins; the trio responsible for removing Gene's original arm; a gorilla wearing a lucha libre wrestling mask and outfit; an android warrior sent by Belze twice to stop Gene; an aspiring rock duo who were originally aspiring musicians that sold their souls to the demons in exchange for power; and a group of dwarfs dressed in Super Sentai-style clothing with playing card emblems on their costumes.

[15] Development was supervised by Shinji Mikami, best known for the Resident Evil series of survival horror games, and was produced by Atsushi Inaba.

[15][16] Mikami expanded this in 2020 saying that the initial concept started sometime in 1999 when he played Final Fight Revenge, a game based on a popular arcade series he liked.

[17] Mikami later approached Inaba with a poster depicting two stylized fists, meant to exemplify the kind of original game he wanted the two to create.

Among minor alterations, such a few signs being changed, the "Chihuahua Curry" power-up was renamed to "Puppy Pizza" in the English localization.

[6] However, another technique called "Head Slicer," which allows the player to decapitate an enemy, was featured in the North American localization, instead of the Japanese one due to CERO censorship policy in Japan.

[6] Masafumi Takada from Grasshopper Manufacture composed the game's soundtrack, with one track contributed by Jun Fukuda.

The score contains many throwbacks to older video game music, and is heavily influenced by 1960s and 1970s theme songs and other genres, including techno, rave, rock and funk.

Takada was told by Mikami that due to the game's hardcore nature, the soundtrack should be composed to "relax things a little bit".

[23] God Hand received almost universal praise for its combat system and an attempt at adhering to an "old-school brawler" formula, attributes which the same critics found to overshadow glaring flaws in its graphics, play control, level design, and camera.

"[47] However, Maxim gave it three stars out of five, saying that it "may lack polish and production values, but like a trailer-park hooker, it still manages to be lovable trash.

Club gave the game a C+ and stated, "Playing this flawed, oddball offering is like flushing your neurotransmitters with Red Bull—painful, mind-expanding, and occasionally laughter-inducing.

[53] Rab Florence of the Scottish television series VideoGaiden claimed God Hand to be one of the best games ever made.

[64] Following Asura's Wrath's release, developer CyberConnect2 revealed that they felt the game would serve to satisfy fans wanting a sequel to God Hand.

[66] God Hand's frantic combat style still persist in games they later released, such as MadWorld, Bayonetta, Metal Gear Rising: Revengeance, and Shinji Mikami's own Vanquish.