The target and mechanism of oral traditional Chinese medicine (TCM) have been important research directions for a long time. The close relationship between osteoporosis and gut microbiota (GM) has been confirmed. However, the relevance of oral TCM and the "Gut-Bone Axis" is still poorly understood.Twenty-one SPF C57BL/6J female mice were divided into sham (Sham), ovariectomized (OVX), and Zuo-Gui-Wan-treated (ZGW, 1.4 g/kg) groups. The osteoporosis mouse model was established through ovariectomy. After eight weeks of Zuo-Gui-Wan treatment via gavage, serum calcium, phosphorus, ALT, AST, CREA, and other biochemical indicators were measured. Subsequently, Micro-CT, HE staining, and analysis of gut microbiota were conducted to further explore the potential mechanism.The anti-osteoporotic effects of ZGW were confirmed through micro-CT, histological, and biochemical tests in an OVX-induced osteoporosis mouse model. ZGW treatment also alters the diversity and composition of the gut microbiota and altered the Firmicutes/Bacteroidetes ratio. Further analysis reveals a correlation between specific bacterial groups and serum indicators. Mfuzz clustering analysis and metagenomeSeq analysis identified important microbiota species that were rescued or modulated by ZGW treatment.These findings suggest that changes in gut microbiota abundance may be linked to ZGW's ability to improve osteoporosis. This study provides new insights into how ZGW treats osteoporosis, though further research is needed to clarify the mechanisms by which specific gut microbiota influence bone health.