Infectious diseases caused by bacterial invasions have imposed a significant global health and economic burden. More worryingly, multidrug-resistant (MDR) pathogenic bacteria born under the abuse of antibiotics have further escalated the status quo. Nowadays, at the crossroads of multiple disciplines such as chemistry, nanoscience and biomedicine, nanozymes, as enzyme-mimicking nanomaterials, not only possess excellent bactericidal ability but also reduce the possibility of inducing resistance. Thus, nanozymes are promising to serve as an alternative to traditional antibiotics. Nanozymes that mimic peroxidase (POD) activity are also known as POD nanozymes. In recent years, POD nanozymes have become one of the most frequently reported and effective nanozymes due to their broad-spectrum bactericidal properties and unique sterilization mechanism. In this review, we introduce the mechanism as well as the classification of POD nanozymes. More importantly, to further improve the antibacterial efficacy of POD nanozymes, we elaborate on three aspects: (1) improving the physicochemical properties; (2) regulating the catalytic microenvironment; and (3) designing multimodel POD nanozymes. In addition, we review the nanosafety of POD nanozymes for discussing their potential toxicity. Finally, the remaining challenges of POD nanozymes and possible future directions are discussed. This work provides a systematic summary of POD nanozymes and hopefully contributes to the early clinical translation.