Osteomyelitis is a severe bone infection caused by bacterial invasion, posing significant therapeutic challenges due to biofilm formation and antibiotic resistance. In recent years, nanozymes-a class of functional nanomaterials with enzyme-like catalytic activities-have shown considerable potential in antimicrobial applications owing to their high stability, tunable catalytic activity, and low tendency to induce resistance, positioning them as promising alternatives to conventional antibiotics. This review systematically examines the therapeutic prospects of nanozyme-based delivery systems for treating osteomyelitis. We detail the antibacterial mechanisms of nanozymes exhibiting various enzyme-mimicking activities-primarily peroxidase-, oxidase-, haloperoxidase-, and hydrolase-like functionalities-such as generating reactive oxygen species (ROS) by catalyzing endogenous hydrogen peroxide and physically degrading biofilm components. This review aims to provide a theoretical foundation and novel insights for developing efficient and safe nanozyme-based antimicrobial agents against osteomyelitis.