Ceria (CeO2) nanozymes have drawn much attention in recent years due to their unique physiochemical properties and excellent biocompatibility. It is therefore very important to establish a simple and robust guideline to regulate CeO2 with desired multi-enzyme-mimicking activities that are ideal for practical bioapplications. In this work, the multi-enzyme-mimicking activities of CeO2 were regulated in a facile manner by a wet-chemical method with different synthesis temperatures. Interestingly, a distinct response in multi-enzyme-mimicking activities of CeO2 was observed towards different synthesis temperatures. And the regulation was ascribed to the comprehensive effect of the oxygen species, size, and self-restoring abilities of CeO2. This study demonstrates that high-performance CeO2 can be rationally designed by a specific synthesis temperature, and the guidelines from radar chart analysis established here can advance the biomedical applications of ceria-based nanozymes.