Like previous games in the series, Professor Layton and the Miracle Mask is a puzzle adventure game split across various chapters. Players explore areas and converse with characters to help solve the mysteries that lay before them. At various points in the game, the player will encounter puzzles that need to be solved. Solving these puzzles earn Picarats, used for accessing bonus content, with more Picarats earned for solving the puzzle without any mistakes. Hint coins can also be found which can be spent to unlock hints to help players solve a puzzle if they get stuck.
There are various changes made during the transition to the Nintendo 3DS, as characters and environments are now presented in 3D graphics. Unlike the previous games, in which players interacted directly with the environment on the touch screen, players now use the touch screen to control a magnifying glass to navigate the environment displayed on the top screen. When the magnifying glass is hovered over something of interest, the player can tap the touch screen to inspect it, initiating conversation with characters or revealing a hint coin or puzzle. Certain areas can be zoomed in to reveal more areas to interact with. Puzzles are still controlled on the touch screen, though many have 3D graphics displayed on the top screen and a few also utilise the 3DS' gyroscope feature. Players are given the option to have reminders of the puzzle description temporarily appear on the bottom screen, or stick it to the top.
Like the previous games before it, Miracle Mask has a set of unique minigames that are expanded upon as the player solves puzzles. 'Toy Robot' tasks the player with navigating a maze in order to reach a goal panel whilst avoiding enemies. 'One-Stop Shop' requires players to arrange items on a shelf based on their type and color in order to entice customers to buy everything on display. 'Rabbit Show' sees Luke taking care of a rabbit and training it to perform in the circus. As Luke converses and trains the rabbit, it learns new actions that must be used accordingly to follow a script in a play. In addition, there is a horse-riding minigame which sees players riding a horse, dodging barrels and collecting carrots to speed up. Midway through the game, there is a top-down adventure portion which sees a young Layton navigating an underground ruin. During this segment, Layton must solve puzzles such as pushing boulders and avoiding mummies, also digging up certain areas to reveal hint coins and hidden puzzles.
Along with the 150 puzzles found in the main game, players are also capable of connecting to Nintendo Network in order to download additional puzzles. These puzzles are made available weekly for a year following release, with seven puzzles made available each week; in all, 365 puzzles can be downloaded. Puzzle packages are downloaded automatically via the Spotpass function of the Nintendo 3DS.