Nanozymes are a class of nanomaterials with enzyme-like activity. Compared with natural enzymes, nanozymes have the advantages of easy synthesis, adjustable activity, and high stability. The nanozymes derived from the metal-organic frameworks (MOFs), as a new family member of nanozymes, have attracted widespread attention due to their rich active sites and controllable catalytic activity. Compared with the traditional nanozymes, MOFs-derived nanozymes maintain the porous structure of MOFs, as well as possess good biocompatibility and high catalytic activity, showing a broad prospect in the biomedical field including tumor catalytic therapy. In this review, we systematically summarize the classification of MOFs-derived nanozymes, including MOFs-derived metal oxides, metal/carbon, metal oxides/carbon, metal sulfide, and single-atom nanozymes (SAzymes). In addition, we also focus on the activity regulation strategies of MOFs-derived nanozymes, such as surface structure regulation, heteroatomic doping, bimetallic construction, and MOFs-based linker exchange strategy. Furthermore, we review the applications of catalytic therapies based on MOFs-derived nanozymes and their synergistic therapies in recent years. Finally, we propose the challenges and prospects of MOFs-derived nanozymes in the biomedical field, to promote the development of MOFs-derived nanozymes and expand their further biomedical application transformation.