Deal or No Deal is based on the TV game show of the same name. The show's host, Howie Mandell, also provides the game's tutorials. The basic gameplay follows the show, in that the player chooses one of twenty-six cases, containing some amount of money from one cent to one million dollars, then they open several other cases. Eventually, a deal is offered by "The Banker", based on the average value of the remaining cases, which the player can either take, or reject to open another batch of cases. Occasionally, after The Banker offers a deal, a minigame may begin, giving the player a chance to earn more cash outside of the main game.

These minigames, which can be played individually in the "Arcade" mode (although in the DS version, they must have been previously played first), include: Ice Breaker, in which the player must quickly remove some ice to reach the frozen case underneath; Shooter, in which the player must shoot cases with positive money values and while avoiding the negative ones; Locker, in which the player must crack a six-digit code for a case; Scale, in which five cases must be weighed among each other, and the player earns cash if their weights match; Memory, a simple memory-matching game; Random, in which the player randomly chooses cases while trying to avoid the empty case (exclusively in the DS version); and Pyramid, in which cases with various values are shuffled around and the player must choose the correct value (exclusively in the Wii version).

In the DS version, all money that the player earns can be spent on the "Showroom", featuring cosmetic unlockables such as cars and houses that can be upgraded with cash. In the Wii version, it is solely for building up a score.