An officially "dead" cop is trained to become an extraordinarily unique assassin in service of the US president.

Remo – Unarmed and Dangerous consists of 6 stages. The very first level, as well as Stage 5, are driving stages, while Stage 4-2 and 6-1 are fighter stages; the rest are standard side-scrolling stages. Each begins with a cinema-style sequence which provides the game's narrative. As usual of the genre, the player has a health gauge and a limited number of lives. Unlimited continues are provided as well.

In the main stages, Remo can switch between one of three weapons: a fist, a foot, and a supply of blue energy waves. Blue energy waves are limited and must be replenished by picking additional supplies dropped by defeated enemies. Other power-ups includes health-restoring heal-aids and meat, as well as coins that will give the player one extra lives for every 100th one collected. In the main segments, Remo can jump, attack, crouch, and climb ladders like in most other action games. He can also run while crouching. In the vehicle stages, the action is viewed from an overhead perspective, Remo will drive a red Porche car, the player maneuvers Remo's car through the road while shifting between three gears and ramming enemy vehicles with the. In the fighting segment, the action is viewed from Remo's perspective, the player moves the target indicator around the moving scenery, shooting the blue energy waves with one button and tossing fists with the other.