AbstractBacterial infection has become one of the leading causes of death worldwide, particularly in low‐income countries. Despite the fact that antibiotics have provided successful management in bacterial infections, the long‐term overconsumption and abuse of antibiotics has contributed to the emergence of multidrug resistant bacteria. To address this challenge, nanomaterials with intrinsic antibacterial properties or that serve as drug carriers have been substantially developed as an alternative to fight against bacterial infection. Systematically and deeply understanding the antibacterial mechanisms of nanomaterials is extremely important for designing new therapeutics. Recently, nanomaterials‐mediated targeted bacteria depletion in either a passive or active manner is one of the most promising approaches for antibacterial treatment by increasing local concentration around bacterial cells to enhance inhibitory activity and reduce side effects. Passive targeting approach is widely explored by searching nanomaterial‐based alternatives to antibiotics, while active targeting strategy relies on biomimetic or biomolecular surface feature that can selectively recognize targeted bacteria. In this review article, we summarize the recent developments in the field of targeted antibacterial therapy based on nanomaterials, which will promote more innovative thinking focusing on the treatment of multidrug‐resistant bacteria.