Natural enzymes play an important role in maintaining normal life activities, but suffer in their inherent instability, harsh reaction conditions and high purification costs, which limit their wide applications in vitro. Compared to natural enzymes, nanozymes with high stability, low cost, and ease of structural regulation and modification attract the great interests and are widely applied to biomedicine, environmental control, industrial production and other fields due to their enzyme-like activities and selectivity. As an essential element and one of the active central metals of natural enzymes in the human body, copper-based (Cu-based) nanozymes have received extensive attentions and researches. This review focused on the classification of Cu-based nanozymes, such as Cu nanozymes, Cu oxide nanozymes, Cu telluride nanozymes, Cu single-atom nanozymes, and Cu-based metal organic framework nanozymes. Then this review described the enzyme-like activities and catalytic mechanisms of Cu-based nanozymes, and also summarized the applications of Cu-based nanozymes, including biosensing, wound healing, acute kidney injury, and tumors. The challenges and future development direction of Cu-based nanozymes were proposed.