Abstract: Antimicrobial resistance (AMR) poses a huge threat to human health. It is urgent to explore efficient ways to suppress the spread of AMR. Antibacterial nanozymes have become one of the powerful weapons to combat AMR due to their enzyme-like catalytic activity with a broad-spectrum antibacterial performance. However, the inherent low catalytic activity of nanozymes limits their expansion into antibacterial applications. In this regard, a variety of advanced chemical design strategies have been developed to improve the antimicrobial activity of nanozymes. In this review, we have summarized the recent progress of advanced strategies to engineer efficient nanozymes for fighting against AMR, which can be mainly classified as catalytic activity improvement, external stimuli, bacterial affinity enhancement, and multifunctional platform construction according to the basic principles of engineering efficient nanocatalysts and the mechanism of nanozyme catalysis. Moreover, the deep insights into the effects of these enhancing strategies on the nanozyme structures and properties are highlighted. Finally, current challenges and future perspectives of antibacterial nanozymes are discussed for their future clinical potential.