Nanozymes, which mimic enzyme functions, have emerged as promising alternatives to natural enzymes for managing metabolic diseases. They possess unique properties such as high catalytic efficiency, stability, cost-effectiveness, and scalability, making them suitable for various applications in medicine, chemical engineering, food, agriculture, and the environment. Nanozymes can regulate reactive oxygen species (ROS), which play a critical role in the development and progression of metabolic diseases. By directly scavenging excess ROS or regulating pathologically related molecules, nanozymes offer a unique therapeutic perspective for metabolic diseases. The review discusses the rational design strategies, cellular-level mechanisms, and therapeutic applications of nanozymes in treating several metabolic diseases, including obesity, diabetes, cardiovascular disease, and diabetic wound healing. It also covers pharmacokinetics, safety analysis, challenges, and future prospects for nanozyme applications. The review highlights the potential of nanozymes in improving disease management through their tunable properties, biocompatibility, and targeted drug delivery capabilities. Nanozymes can be designed to have specific catalytic activities, such as peroxidase (POD)-, superoxide dismutase (SOD)-, oxidase (OXD)-, and catalase (CAT)-like activities. These activities are crucial in alleviating diseases related to oxidative stress and have shown promise in providing new treatment strategies for cardio- and cerebrovascular diseases. The material selection for nanozymes involves choosing materials with high catalytic activity and the ability to be modified for specific applications. Common materials include metal nanoparticles, metal oxides, carbon-based materials, and metal-organic frameworks (MOFs). Surface functionalization of nanozymes involves modifying their surfaces with specific functional groups or molecules to enhance their catalytic activity, stability, selectivity, and biocompatibility. This process allows for the targeted delivery of therapeutic agents to specific sites. Size and shape control of nanozymes are also important factors in their performance, as smaller nanoparticles can penetrate tissues more effectively but may have a shorter half-life in the bloodstream. Organ-specific targeting strategies for nanozymes involve directing these nanomaterials toward specific organs in the body. This can be achieved through surface modification, functionalization, and encapsulation techniques. For example, nanozymes modified with ligands can target the liver, adipose tissue, or pancreas, enhancing their therapeutic efficacy. The therapeutic mechanisms of nanozymes in metabolic diseases include modulation of glucose uptake, facilitation of glycogen synthesis, and reduction of inflammation and insulin resistance. Nanozymes have shown potential in improving insulin sensitivity and reducing insulin resistance, which are critical factors in the management of diabetes. Additionally, nanozymes have demonstrated anti-inflammatory and antioxidant properties, which are essential in the treatment of metabolic diseases. The application of nanozymes in metabolic disease management includes their use in treating obesity, diabetes, cardiovascular disease, and diabetic wound healing. These applications highlight the versatility and potential of nanozymes in improvingNanozymes, which mimic enzyme functions, have emerged as promising alternatives to natural enzymes for managing metabolic diseases. They possess unique properties such as high catalytic efficiency, stability, cost-effectiveness, and scalability, making them suitable for various applications in medicine, chemical engineering, food, agriculture, and the environment. Nanozymes can regulate reactive oxygen species (ROS), which play a critical role in the development and progression of metabolic diseases. By directly scavenging excess ROS or regulating pathologically related molecules, nanozymes offer a unique therapeutic perspective for metabolic diseases. The review discusses the rational design strategies, cellular-level mechanisms, and therapeutic applications of nanozymes in treating several metabolic diseases, including obesity, diabetes, cardiovascular disease, and diabetic wound healing. It also covers pharmacokinetics, safety analysis, challenges, and future prospects for nanozyme applications. The review highlights the potential of nanozymes in improving disease management through their tunable properties, biocompatibility, and targeted drug delivery capabilities. Nanozymes can be designed to have specific catalytic activities, such as peroxidase (POD)-, superoxide dismutase (SOD)-, oxidase (OXD)-, and catalase (CAT)-like activities. These activities are crucial in alleviating diseases related to oxidative stress and have shown promise in providing new treatment strategies for cardio- and cerebrovascular diseases. The material selection for nanozymes involves choosing materials with high catalytic activity and the ability to be modified for specific applications. Common materials include metal nanoparticles, metal oxides, carbon-based materials, and metal-organic frameworks (MOFs). Surface functionalization of nanozymes involves modifying their surfaces with specific functional groups or molecules to enhance their catalytic activity, stability, selectivity, and biocompatibility. This process allows for the targeted delivery of therapeutic agents to specific sites. Size and shape control of nanozymes are also important factors in their performance, as smaller nanoparticles can penetrate tissues more effectively but may have a shorter half-life in the bloodstream. Organ-specific targeting strategies for nanozymes involve directing these nanomaterials toward specific organs in the body. This can be achieved through surface modification, functionalization, and encapsulation techniques. For example, nanozymes modified with ligands can target the liver, adipose tissue, or pancreas, enhancing their therapeutic efficacy. The therapeutic mechanisms of nanozymes in metabolic diseases include modulation of glucose uptake, facilitation of glycogen synthesis, and reduction of inflammation and insulin resistance. Nanozymes have shown potential in improving insulin sensitivity and reducing insulin resistance, which are critical factors in the management of diabetes. Additionally, nanozymes have demonstrated anti-inflammatory and antioxidant properties, which are essential in the treatment of metabolic diseases. The application of nanozymes in metabolic disease management includes their use in treating obesity, diabetes, cardiovascular disease, and diabetic wound healing. These applications highlight the versatility and potential of nanozymes in improving