Background Gushukang (GSK) capsule is a Chinese patent medicine for the treatment of osteoporosis (OP). It has been widely used in clinics. However, the specific mechanism and target of GSK in the treatment of osteoporosis is not clear, which needs further study. Methods Metabolomics (GC/MS) and proteomics (TMT-LC-MC/MC) together with bioinformatics (KEGG pathway enrichment), correlation analysis (pearson correlation matrix) and joint pathway analysis (Metabo Analyst) were employed to discover the underlying mechanisms of GSK. Results The regulations of differential proteins Cant1, Gstz1, Aldh3b1, Bid and Slc1a3 in the common metabolic pathway of differential proteins and metabolites between GSK/OP and OP/SHAM were corrected in GSK group. The regulations of 12 metabolites (Tyramine、Thymidine、Deoxycytidine、Cytosine、L-Aspartate and so on) were differential in the common enrichment metabolic pathway between GSK /OVX and OVX/SHAM. Differential proteins and metabolites jointly regulate 11 metabolic pathways, such as purine metabolism, pyrimidine metabolism, histidine metabolism, beta-Alanine metabolism and so on. Conclusion GSK may protect bone metabolism in osteoporosis rats by affecting nucleotide metabolism, amino acid metabolism and immune system.