Cerium oxide nanoparticles, due to their excellent catalytic activities, have emerged as promising biological nanoenzymes. The redox reactions between Ce³⁺ and Ce⁴⁺ ions lead to the formation of oxygen vacancies in the lattice structure, which can mimic various enzyme activities such as catalase, superoxide dismutase (SOD), peroxidase, and oxidase. These nanoparticles exhibit significant antioxidant properties and have been widely applied in biomedicine, disease diagnosis, and treatment. This review provides a comprehensive overview of the catalytic mechanisms and multiple enzyme activities of cerium oxide nanoparticles, along with their potential applications in treating diseases related to oxidative damage, including brain, bone, nerve, and blood vessel disorders. The review also discusses the challenges and future directions in the clinical application of cerium oxide nanoparticles, emphasizing the need for further research on toxicity, surface modification, and immune responses.Cerium oxide nanoparticles, due to their excellent catalytic activities, have emerged as promising biological nanoenzymes. The redox reactions between Ce³⁺ and Ce⁴⁺ ions lead to the formation of oxygen vacancies in the lattice structure, which can mimic various enzyme activities such as catalase, superoxide dismutase (SOD), peroxidase, and oxidase. These nanoparticles exhibit significant antioxidant properties and have been widely applied in biomedicine, disease diagnosis, and treatment. This review provides a comprehensive overview of the catalytic mechanisms and multiple enzyme activities of cerium oxide nanoparticles, along with their potential applications in treating diseases related to oxidative damage, including brain, bone, nerve, and blood vessel disorders. The review also discusses the challenges and future directions in the clinical application of cerium oxide nanoparticles, emphasizing the need for further research on toxicity, surface modification, and immune responses.