Abstract: Overprescription and abuse of antibiotics have led to the development of drug-resistant strain. However, the number of antimicrobial drugs in the current R&D pipelines is too small, increasing the demand for the R&D of drugs against resistant bacteria. At the same time, new technologies are urgently needed to accelerate the development process. Computer-aided drug design (CADD) has been successfully applied in the R&D of anti-viral and anti-tumor drugs such as the marketed drugs zanamivir and imatinib. In addition, its application in the R&D of drugs against resistant bacteria has attracted great attention. The paper reviewed the structure-based and ligand-based drug discovery methods and briefly introduced the application of virtual high-throughput screening, protein structure prediction methods, protein-ligand docking, pharmacophore model and QSAR technology in the discovery of drugs against resistant bacteria.