Nanozymes have attracted much attention in the field of environmental remediation due to their excellent catalytic activity. Elemental doping can improve the catalytic performance of nanozymes. A highly active copper-doped manganese dioxide(Cu-MnO2) oxidase-like nanozyme(referred to oxidase-like enzyme) was prepared by a one-step hydrothermal method, and its degradation of rhodamine B (RhB) dye was investigated. It has been shown that the catalytic activity of Cu-MnO2 is enhanced by the synergistic effect of Cu-MnO2 upon copper doping. With a solution pH of 3, an initial mass concentration of RhB of 50 mg/L, and a dose Cu-MnO2 dosage of 0.01 g, RhB was fully degraded within 30 min, and the degradation rate of RhB was still 75% after 5 times the catalyst used. In addition, the degradation rates of ciprofloxacin, ofloxacin, tetracycline, and hydroquinone were 88.86%, 90.47%, 92.62% and 90.99%, respectively. The mechanism of catalytic degradation of RhB by Cu-MnO2 oxidase-like enzyme showed that there were abundant holes (h+) in Cu-MnO2 rich in oxygen vacancies, which was beneficial for adsorbing and catalyzing dissolved oxygen to produce a large amount of singlet oxygen (1O2) and a small number of superoxide radicals (O2·-) and other reactive oxygen species for the rapid degradation of organic pollutants.