Nanozymes, a kind of nanoparticles with enzyme-mimicking activities, have attracted considerable attention due to their robust catalytic properties, ease of preparation, and resistance to harsh conditions. By combining nanozymes with surface-enhanced Raman spectroscopy (SERS) technology, highly sensitive and selective sensors have been developed. These sensors are capable of detecting a wide range of analytes, such as foodborne toxins, environmental pollutants, and biomedical markers. This review provides an overview of recent advancements in the synthesis and surface modification of nanozymes, highlighting their ability to mimic multiple enzymes and enhance catalytic performance. In addition, we explore the development and applications of nanozyme-based SERS sensors in food contaminants, environmental pollutants, and biomedical markers. The review concludes with perspectives and challenges facing the field, involving the need for deeper understanding of nanozyme principles and mechanisms, development of standardized systems for characterization, and the engineering of nanozymes with tailored properties for specific applications. Finally, we discuss the potential for integrating various techniques with nanozymes to create multi-modal detection platforms, paving the way for the next generation of analytical tools in the fields of food safety, environmental monitoring, and biomedical diagnostics.