Copper (Cu), an indispensable trace element within the human body, serving as an intrinsic constituent of numerous natural enzymes, carrying out vital biological functions. Furthermore, nanomaterials exhibiting enzyme-mimicking properties, commonly known as nanozymes, possess distinct advantages over their natural enzyme counterparts, including cost-effectiveness, enhanced stability, and adjustable performance. These advantageous attributes have captivated the attention of researchers, inspiring them to devise various Cu-based nanomaterials, such as copper oxide, Cu metal-organic framework, and CuS, and explore their potential in enzymatic catalysis. This comprehensive review encapsulates the most recent advancements in Cu-based nanozymes, illuminating their applications in the realm of biochemistry. Initially, it is delved into the emulation of typical enzyme types achieved by Cu-based nanomaterials. Subsequently, the latest breakthroughs concerning Cu-based nanozymes in biochemical sensing, bacterial inhibition, cancer therapy, and neurodegenerative diseases treatment is discussed. Within this segment, it is also explored the modulation of Cu-based nanozyme activity. Finally, a visionary outlook for the future development of Cu-based nanozymes is presented.