Bone metastasis is a common complication in patients with advanced tumors, causing pain and bone destruction and affecting their quality of life. Typically, complementary and alternative medicine (CAM), with unique theoretical guidance, has played key roles in the treatment of tumor-related diseases. Gu-tong formula (GTF), as a representative prescription of traditional Chinese medicine, has been demonstrated to be an effective clinical medication for the relief of cancer pain. However, the molecular mechanism of GTF in the treatment of osteolytic metastasis is still unclear. Herein, we employ network pharmacology and molecular dynamics methods to uncover the potential treatment mechanism, indicating that GTF can reduce the levels of serum IL6 and TGFB1 and thus limit the scope of bone cortical damage. Among the active compounds, sesamin and deltoin can bind stably with IL6 and TGFB1, respectively, and have the potential to become anti-inflammatory and anticancer drugs. Although the reasons for the therapeutic effect of GTF are complex and comprehensive, this work provides biological plausibility in the treatment of osteolytic metastases, which has a guiding significance for the treatment of cancer pain with CAM.