The problem of marine biofouling persists in marine resource development, particularly for marine observation. While nanomaterials with enzyme-mimicking activity show promise in combating marine biofouling, their unique physicochemical properties that enable nanozymes with multiple enzymatic activities for a synergetic antifouling effect have yet to be explored. Here, it is shown that a transparent zwitterionic coating based on Ag/Ag2S Janus nanoparticles (Ag/Ag2S JNPs) with peroxidase-, light-activated oxidase-, and haloperoxidase-mimicking activities contributes to antifouling synergy. The mechanism of the nanozyme action is revealed in a detailed experimental and computational study, in which unique Janus structures guarantee multi-enzyme-mimicking properties and produce [rad]OH, HOBr, and O2[rad]− to combat biofouling. Through the formation of hydration layers, zwitterionic coatings further enhance this antifouling capacity, as demonstrated by both indoor and outdoor marine field antifouling tests. Consequently, a coating like this shows a clear transmittance and excellent antifouling ability after 90 days in marine immersion, reducing fouling by 74.91 % and 39.71 % compared to a control coating and a commercial coating, respectively. This study not only demonstrates synergetic antifouling actions via multi-enzyme-mimicking activities but also uncovers a new paradigm in nanozyme-based environmentally friendly, sustainable antifouling strategy.