This review discusses the recent progress and prospects of metal–organic framework (MOF)-based nanozymes in biomedical applications. Nanozymes are nanoscale materials that exhibit enzyme-like properties, offering advantages such as low preparation costs, robust catalytic activity, and long-term stability. MOFs, with their unique composition, adaptable pore size, structural diversity, and tunable physicochemical properties, have emerged as promising candidates for nanozyme development. The review highlights the various enzyme-mimetic activities of MOFs, including peroxidase (POX), oxidase (OX), superoxide dismutase (SOD), and catalase (CAT) activities, and discusses strategies to enhance their catalytic activity through modification and functionalization. Applications of MOF-based nanozymes in biosensing and therapeutics are also explored, including colorimetric, fluorescence, and electrochemical biosensors, as well as cancer therapy, photothermal therapy, photodynamic therapy, anti-inflammatory, and antimicrobial treatments. The review concludes by addressing challenges and future directions in the field, emphasizing the need for interdisciplinary efforts to advance the development of MOF-based nanozymes.This review discusses the recent progress and prospects of metal–organic framework (MOF)-based nanozymes in biomedical applications. Nanozymes are nanoscale materials that exhibit enzyme-like properties, offering advantages such as low preparation costs, robust catalytic activity, and long-term stability. MOFs, with their unique composition, adaptable pore size, structural diversity, and tunable physicochemical properties, have emerged as promising candidates for nanozyme development. The review highlights the various enzyme-mimetic activities of MOFs, including peroxidase (POX), oxidase (OX), superoxide dismutase (SOD), and catalase (CAT) activities, and discusses strategies to enhance their catalytic activity through modification and functionalization. Applications of MOF-based nanozymes in biosensing and therapeutics are also explored, including colorimetric, fluorescence, and electrochemical biosensors, as well as cancer therapy, photothermal therapy, photodynamic therapy, anti-inflammatory, and antimicrobial treatments. The review concludes by addressing challenges and future directions in the field, emphasizing the need for interdisciplinary efforts to advance the development of MOF-based nanozymes.