The game is based on Go Nagai's manga, that was later made into anime TV series. Rather than following the plot of the manga, the game has the player assume the role of a nameless male detective, who is headed to a fictional country called Austral Island in search of a missing girl. When the hero arrives on the island, he soon discovers that there is some sort of a supernatural organization that might be the reason for the girl's disappearance. Then he hooks up with Honey Kisaragi, the heroine of the manga and TV series, who is an android that can assume various combat forms and fight evil creatures.

This is an adventure game with simple interaction (point-and-click), the cursor turning blue for looking at objects and yellow for using them or talking to people. At some screens there are multiple dialogue choices. There are no puzzles in the game, but sometimes the player controls Honey in combat sequences, which play like a mini-game that involves pressing a button as many times as possible within a time limit, and choosing vulnerable spots on the enemy's body to execute attacks. There is also a map of the island which the player can navigate the main character on.

Unlike many other Japanese adventures, characters are animated on almost every screen in Cutey Honey FX, and a large portion of the game is occupied by anime-style movies.