In Sports mode, players must knock a ball into an opponent's goal, with different types of balls having different properties, such as soccer balls being unable to be grabbed. The game also features a single-player arcade mode and a 'Sports' mode, based on the 'Slap Ball' game type from the developer's previous fighting game Slap City. The game supports local and online multiplayer for up to four players, with the game's online functionality utilizing rollback netcode on supported platforms. and The Assist Box is Similar to Assist Trophies in Super Smash Bros.

Introduced The Slimetime Blast! is a Similiar to Super Smash Bros.' Final Smash. As characters take damage, the amount of knockback caused by opponents' attacks will increase, making them easier to knock off the stage. Unique to the game is the 'strafe' function, where players can hold a button to prevent their character from turning around while moving in different directions this can be used to continue attacking an opponent while actively retreating from them. Players can also grab and throw opponents or enemy projectiles, even in the air, and guard against attacks without penalty, though they will be pushed back in doing so. Different attacks can be performed by pushing up or down or running in combination with one of the three attack buttons. Characters have three different types of attacks: light attacks, which are weak but quick and can be used to perform combos strong attacks, which are slower but do more damage and knock opponents back further and special attacks, the properties of which vary by character. Movement takes place on a two-dimensional plane, with characters able to move around by running, jumping, double-jumping, or performing a mid-air dash in any of eight directions. Each stage offers a different layout, with some also having additional hazards that can cause damage to the characters. Nickelodeon All-Star Brawl 2 is a platform fighter, with players battling on different stages and attempting to knock their opponents outside the boundaries of the arena.

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