Catalytic nanoparticles (CNPs) as heterogeneous catalyst reveals superior activity due to their physio‐chemical features, such as high surface‐to‐volume ratio and unique optical, electric, and magnetic properties. The CNPs, based on their physio‐chemical nature, can either increase the reactive oxygen species (ROS) level for tumor and antibacterial therapy or eliminate the ROS for cytoprotection, anti‐inflammation, and anti‐aging. In addition, the catalytic activity of nanozymes could specifically trigger a specific reaction accompanied by the optical feature change, presenting the feasibility of biosensor and bioimaging applications. Undoubtedly, CNPs play a pivotal role in pushing the evolution of technologies in medical and clinical fields, and advanced strategies and nanomaterials rely on the input of chemical experts to develop. Herein, we present a systematic and comprehensive review of the challenges and recent development of catalytic NPs for biomedical applications from the viewpoint of advanced nanomaterial with unique catalytic activity and additional functions. Furthermore, we critically discuss the biosafety issue of applying biodegradable and non‐biodegradable nanozymes and future perspectives to guide a promising direction in developing span‐new nanozymes and more intelligent strategies for overcoming the current clinical limitations.This article is protected by copyright. All rights reserved