Objective To explore the possible mechanism of Honeysuckle and Astragalus in the treatment of osteomyelitis by using the method of network pharmacology and molecular docking, so as to provide scientific basis for clinical medication. Methods The bioactive components of Honeysuckle and Astragalus were searched in TCMSP platform and screened according to the research needs. At the same time, the potential targets of osteomyelitis were searched in protein database and related gene database, and the common targets were found in Venny diagram; The complex network diagram of "drug composition-target-disease" is constructed by using Cytoscape software. Protein interaction analysis, target gene function enrichment analysis and signal pathway analysis are carried out by Bisogenet software, CytoNCA software and Metascape database. The core target is connected with the compound by using molecular docking software (AutoDock), The results were visualized by Pymol. Results 236 kinds of effective bioactive components of Honeysuckle and 87 kinds of effective components of Astragalus were explored, and 21 possible common targets were predicted. Enrichment analysis showed that Honeysuckle and Astragalus could affect the expression of a variety of proteins, which were closely related to the occurrence and development of osteomyelitis. The results of molecular docking showed that the effective components of Honeysuckle and Astragalus could spontaneously bind to the target protein. Conclusion Honeysuckle and Astragalus can play a therapeutic role in four aspects: antioxidant stress, improving immunity, reducing apoptosis, anti-inflammatory and antibacterial, which provides a theoretical basis for the follow-up treatment of osteomyelitis and the development of new drugs.