The boom in nanotechnology brings new insights into the development of artificial enzymes (nanozymes) with ease of modification, lower manufacturing cost, and higher catalytic stability than natural enzymes. Among various nanomaterials, two-dimensional (2D) nanomaterials exhibit promising enzyme-like properties for a plethora of bioapplications owing to their unique physicochemical characteristics of tuneable composition, ultrathin thickness, and huge specific surface area. Herein, we review the recent advances in several 2D material-based nanozymes, such as carbonaceous nanosheets, metal-organic frameworks (MOFs), transition metal dichalcogenides (TMDs), layered double hydroxides (LDHs), and transition metal oxides (TMOs), clarify the mechanisms of peroxidase (POD)-mimicking catalytic behaviors, and overview the potential bioapplications of 2D nanozymes.