There are many Regional differences between the Japanese and U.S. versions of Super Smash Bros. Melee. They include name changes (Jigglypuff is named Purin and Bowser is named Koopa in the Japanese version), event names ("Time for a Check Up" is "Don't Hog The Spotlight, Bro" in Japan), and different names for items (Bob-Omb is Bomb Soldier in Japan).

The main character of the game Devil World, Tamagon, appeared as a trophy in the Japanese version of Super Smash Bros. Melee. Tamagon was removed in the American version of the game but the trophy can still be found with Action Replay, complete with a translated description. Stranger still, the Tamagon trophy was removed outright from the European version of the game and cannot even be found with a cheat device, despite the fact that Devil World was released in European countries.

In early versions of the game, the Princess Daisy trophy contains a third eye beneath her hair if viewed at the right angle. In fact, there are many hidden eyes all over her head, but this is the only abnormal eye that can be seen in normal play.

Hideo Kojima had requested that Metal Gear Solid's Solid Snake be in the game, but due to time constraints he couldn't be added to the game's roster. Sonic the Hedgehog also nearly made it into the game. Sonic's creator Yuji Naka stated that Sonic was going to be in Melee, but he also was cut due to time constraints. Both characters later made it into the sequel, Super Smash Bros. Brawl.

Despite being a boss character, Master Hand is considered worse than any regular character in competitive play when unlocked through the Name Entry glitch. This is due to his high power and unconventional win conditions being nullified by his lack of defense options, slow attack and non-existent movement speed, and - in the case of doubles - his inability to attack the member of the opposing team with a lower port number.

Due to Master Hand being an undesirable character to play as, he is rarely explicitly mentioned as being banned in Melee tournament rulesets. However, he will usually be banned at a TO's discretion in the rare occasion he pops up, due to his win conditions stretching matches out extremely long and his matches always ending with the game crashing.