Infectious diseases caused by bacteria represent a global threat to human health. However, due to the abuse of antibiotics, drug-resistant bacteria have evolved rapidly and led to the failure of antibiotics treatment. Alternative antimicrobial strategies different to traditional antibiotics are urgently needed. Enzyme-based antibacterials (Enzybiotics) have gradually attracted interest owing to their advantages including high specificity, rapid mode-of-action, no resistance development, etc. However, due to their low stability, potential immunogenicity, and high cost of natural enzymes, enzybiotics have limitations in practical antibacterial therapy. In recent years, many nanomaterials with enzyme-like activities (Nanozymes) have been discovered as a new generation of artificial enzymes and perform catalytic antibacterial effects against bacterial resistance. To highlight the progress in this field of nanozyme-based antibacterials (Nanozybiotics), this review discussed the antibacterial mechanism of action of nanozybiotics with a comparison with enzybiotics. We propose that nanozybiotics may bear promising applications in antibacterial therapy, due to their high stability, rapid bacterial killing, biofilm elimination, and low cost.