The goal of Palamedes is to clear the screen, which is line by line filling up with dice. Players control a small person situated near the bottom of the screen, who can only be moved to the left or right. The number of the dice the person is holding can be changed with the B button, pressing the A button will shoot the dice upwards. If the die hits another one with a matching number, the targeted dice disappears from the playing area and is added to a column at the bottom of the screen. Pressing down after lining up at least three dice of either the same number or consecutive numbers in the bottom row will destroy up to five lines at once.
The gameplay involves using the B button to change the dice, A button to shoot them upwards and pressing down to clear lines. The game has different modes of play, including single player, tournament mode where players duel CPU opponents and two-player mode for competitive play against a friend.