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The escalating threat of antimicrobial resistance (AMR) and the limited efficacy of conventional antibiotics have intensified the search for alternative therapeutic strategies. Nanozymes, nanomaterials with enzyme-mimicking properties, have emerged as a promising class of antimicrobial agents due to their broad-spectrum activity, tunable catalytic functions, and resistance-independent mechanisms. This review provides a comprehensive overview of the recent advances in nanozyme-based antimicrobial applications, focusing on their classification, catalytic mechanisms, and multifaceted antimicrobial actions. We highlight the unique advantages of nanozymes, including their ability to generate reactive oxygen species (ROS), disrupt biofilms, modulate infection microenvironments, and synergize with other therapeutic modalities. Furthermore, we discuss their performance in various infection models, such as skin and soft tissue infections, oral infections, ocular infections, gastrointestinal infections, respiratory infections, urinary tract infections, systemic infections, diabetic wounds, chronic ulcers, and fungal infections. Finally, we address current challenges in clinical translation, including biosafety, dose control, and scalable production. This review underscores the transformative potential of nanozymes in combating drug-resistant pathogens and offers insights into future directions for their clinical development.