Drug-resistance bacterial and biofilm-related infectious diseases pose a significant threat to the global public health. Focusing on the drug-resistance mechanisms of bacteria to antibiotics, we aim at presenting the research progress of nanomaterial-based antibacterial agents. This review starts with clarifying nanomaterials with unique physicochemical characteristics, which act as intrinsic antibacterial agents. Subsequently, we discuss nanomaterial-based artificial enzymes, which can kill bacteria with reactive oxygen species (ROS). Furthermore, nanomaterial-based multiple synergetic modality nanoplatforms are constructed to combat infections. These multifunctional antibacterial agents, either microenvironment-oriented or external stimulants responsive, coordinate new treatments for precise medication and integration of diagnoses and treatments. In addition, the challenges and clinical prospects of these nanomaterial-based antibacterial agents are discussed, providing new perspectives of developing safer and more efficient antibacterial agents.