Jewels of Cleopatra is a match-three game with an Egyptian archaeology theme. Each stage is a chamber of a temple, where the objective is to create a path to the exit for Dr.Felicity Tumstone, the Indiana Jones-style female main character. She can only walk on gilded tiles, and each successful match makes the background gold eventually allowing her to escape.
The default way-point is the tomb's exit, but the player can set it to any place by clicking on the mini-map at the bottom-right. Matches can be performed independently from the character's movement, as she moves automatically using the shortest route possible.
There are some mini-games between stages. Jigsaws must be assembled within a time limit, and a scarab races must be won where a mouse-controlled bug is guided by the player.
Several enemies and obstacles appear on more advanced stages. Scorpions, snakes, and mummies attack Tumstone, restarting the level. Locusts change the tiles back to stone. Spiders lock Felicity and some of the tiles with their web. Rocks block the way, and cannot be matched. At the end of each temple, there is a challenge where Tumstone must reach the exit before a thief called Shady McGrady to win an artifact.
Power-ups are available inside chests on some levels. They can also be awarded by winning the races or making five-tile matches. Gold tiles and gold blocks transform stone tiles in to gold. Column and row breakers destroy columns and rows of tiles. The exorcism makes the mummies disappear. The dynamite stack explodes a square of nine tiles. A can of insecticide spray kills all the bugs, and the pick-axe breaks the rocks.