Objective: To investigate the therapeutic effects of friedelin in the treatment of osteoporosis, with a focus on its regulatory role in osteogenic differentiation and bone metabolism. Methods: CCK-8, ALP staining, ARS staining, and RT-qPCR were used to detect the effect of Friedelin on the cell activity and osteogenic differentiation of human mesenchymal stem cells (hMSCs). Network pharmacology, GO/KEGG enrichment analysis, molecular docking, and luciferase reporter assay were employed to explore its molecular mechanism. C57BL/6 mice and ovariectomized (OVX) mouse models were used to evaluate its in vivo biosafety and therapeutic effect. Results: Friedelin had no obvious cytotoxicity on hMSCs, and its efficacy in promoting osteogenic differentiation was superior to that of risedronate sodium (P<0.05). 52 common targets of Friedelin and osteoporosis were screened out, with 6 key targets including INS, EGFR, EGR1, PTGS2, CYP3A4, and CYP19A1, among which CYP19A1 had the most stable binding with Friedelin. Friedelin could activate transcription factors such as RUNX2, and its targets were enriched in prolactin, FoxO and other related pathways. Its intragastric administration had good safety and could improve the bone microstructure of OVX mice, with a therapeutic effect superior to that of risedronate sodium (P<0.05). Conclusion: Friedelin has good in vivo biosafety and significant anti-osteoporotic efficacy. With CYP19A1 as the core target, it regulates osteogenic differentiation and bone metabolism balance through multiple targets and pathways, and is expected to become a new candidate drug for osteoporosis.