Objective To screen genes and potential therapeutic drugs related to osteoporosis (OP) based on CMap database, and to provide a new idea for the treatment of OP.Methods The chips related to OP in GEO database were searched and the differential genes were analyzed by R. The public databases of disease genes were searched. The related pathogenic genes of OP were obtained. The key targets of OP were obtained, and the network of proteinprotein interaction (PPI) was constructed. The GO and KEGG pathway were analyzed by DAVID database, and the small molecular compounds of negative correlation were screened out by connectivity map (CMap) database.Results The chip of GSE56116 was screened out from GEO database, and 69 upregulated genes and 106 downregulated genes were screened by R. By searching GAD, TTD, OMIM, DrugBank, PharmGKB and DisGeNET databases, 691 known targets related to the pathogenesis of OP were obtained, and 14 key genes of OP were obtained. The results of enrichment analysis by DAVID database showed that the key targets of OP were mainly related to immune response, reaction to hydrogen peroxide, antigen processing and presentation. The results of CMap database showed that digoxin, hesperidin and other small molecular compounds had high negative correlation.Conclusion With the application of bioinformatics and CMap database, it is found that small molecular compounds such as digoxin and hesperidin may be candidates for the treatment of OP. Besides, this research method provides a new way and train of thought for finding candidate therapeutic drugs for diseases. 