OBJECTIVE： To investigate the mechanism of Drynariae rhizoma in the treatment of osteoporosis （OP）. METHODS： The active compounds and targets of D. rhizoma were obtained by using Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM database）. The targets of relevant compounds were also obtained by GeneCards database， and targets of D. rhizoma were obtained by the combination of the two. The disease targets corresponding to OP were obtained by using TTD， DrugBank， OMIM， GAD， PharmGKB and CTD database. The D. rhizoma-OP disease intersection targets were obtained after intersecting with the target of D. rhizoma. PPI network was constructed by STRING online database， analyzed by using Cytoscape 3.6.1 software to obtain key targets and showed by network visualization. Gene ontology（GO） analysis of drug-disease intersection target were conducted by DAVID online tools. KEGG pathway enrichment analysis was conducted by KOBAS online tools to screen the significant enrichment pathway （P＜0.05）. The key genes were screened by MCC algorithm. RESULTS： There were 7 active compounds of D. rhizoma 136 intersection targets of D. rhizoma-OP disease. GO analysis results showed that the biological function of intersection target mainly included chemical reaction， steroid metabolic process as well as cellular response to chemical stimulus and so on； cell composition mainly included extracellular space， extracellular area and cytoplasm；molecular functions included heme binding， tetrapyrrole binding and monooxygenase activity， etc. KEGG pathway enrichment showed that above targets were mainly related to bone metabolism， endocrinology， inflammation， tumor， apoptosis， etc. Thirty key genes （such as ALB， AKT1， JUN， etc.， P≤1.96×10－9） were screened by MCC algorithm. CONCLUSIONS： The mechanism of action of D. rhizoma in the treatment of OP is in multi-target and multi-system manner. In addition to influencing the related pathways of bone metabolism， it can also affect various metabolic pathways in vivo.