Antibiotic therapy is the most powerful strategy for treating bacterial infections in clinic. However, antibiotic resistance has become one of the biggest threats to public health worldwide due to the misuse and abuse of antibiotics. What is worse, the speed of the discovery of new antibiotics is largely hysteretic compared to the growth of antibiotic resistance. The world is on the threshold of the "post-antibiotic era". Nanomaterials have shown great potential in restoring the antibacterial activity of conventional antibiotics by different mechanisms, including optimizing pharmacokinetics, improving antibiotic internalization, interfering with bacterial metabolism, enhancing biofilm penetration, changing biofilm microenvironments, and so on. The combination of nanotechnology and antibiotics would be the most promising strategy to cope with antibiotic-resistant bacteria. In this review, the mechanisms of antibiotic resistance are introduced and the recent strategies for improving the therapeutic efficacy of antibiotics to combat drug resistance using nanomaterials are summarized. The advantages and mechanisms of nanoparticle-based antibiotics are overviewed as well. Moreover, the challenges of nano-antibiotics in clinical applications have also been discussed.