Objective Based on the theory of “kidney essence-bone metabolism”, to explore the mechanism of Taohong Siwu Tang in improving diabetes induced osteoporosis(DOP) by regulating RANKL/OPG signal pathway, and analyze its multi target synergy.Methods 60 SPF grade SD rats were selected, with 12 as the blank group. The remaining rats were used to establish a DOP model and randomly divided into a model group and low, medium, and high-dose treatment groups with Taohong Siwu Tang, with 12 rats in each group. The treatment group was given corresponding doses of Taohong Siwu Tang by gavage, while the blank group and model group were given equal volumes of physiological saline by gavage for 12 weeks. Detect the levels of bone metabolism markers (ALP, OCN, TRAP) and inflammatory factors (TNF-α, IL-6) in serum by ELISA. TUNEL staining was used to detect the apoptosis rate of bone tissue cells. Western blot and qPCR were used to measure the protein and mRNA expression levels of RANKL and OPG in bone tissue. The criticality of the RANKL/OPG pathway through in vitro cell experiments were verified.Results Compared with the model group, the treatment group with Taohong Siwu Tang significantly improved the levels of ALP, OCN, and TRAP in rats (P<0.05), while the levels of TNF-α and IL-6 decreased (P<0.05). TUNEL staining showed a decrease in apoptosis rate of bone tissue cells; Western blot and qPCR results showed that the protein and mRNA expression of RANKL decreased (P<0.05), while the protein and mRNA expression of OPG increased (P<0.05), with the high-dose group showing the most significant effect (P<0.01). In vitro experiments showed that RANKL induction significantly increased the number of TRAP+cells, increased RANKL protein expression, decreased OPG protein expression, and increased the RANKL/OPG ratio(P<0.05). The intervention of Taohong Siwu Tang significantly reduced the number of TRAP+cells, decreased the expression of RANKL protein, increased the expression of OPG protein, and reduced the RANKL/OPG ratio(P<0.01). Overexpression of OPG significantly increased ALP activity, Runx2, and OCN mRNA expression(P<0.05), while the combination of OPG overexpression and Taohong Siwu Tang group showed significantly higher ALP activity, Runx2, and OCN mRNA expression than the OPG overexpression group(P<0.01).Conclusion Taohong Siwu Tang significantly improves bone metabolism in DOP rats by regulating the RANKL/OPG signaling pathway, reducing the expression of inflammatory factors and cell apoptosis. Its mechanism of action is closely related to multi-target synergistic effects