While oxidases play crucial roles in the cell metabolism by efficient and selective utilization of O2, the practical applications of natural oxidases are limited due to their intrinsic shortcomings (high cost in purification and poor stability). Recently, great varieties of engineered nanostructures have been demonstrated to display oxidase-mimetic activity, which can serve as ideal candidates for oxidase-mimicking nanozymes. In view of the significant progress of nanozymes, we, in this review, systematically illustrate the classification of oxidase-mimicking nanozymes in terms of the acting group of representative substrates and discuss their possible catalytic mechanisms. We also summary the activity modulation of oxidase-mimicking nanozymes by tuning the physicochemical property of nanomaterials and surrounding environments, as well as their potential biomedical applications in biosensing, antibacteria and cancer treatment. Finally, the current opportunities and challenges are discussed to stimulate the research of understanding and development of nanozymes.