Osteosarcoma (OS) is a common primary malignant bone tumor with high mortality, disability, metastasis, and recurrence rates and a complex pathogenesis, Resulting in serious effects on patient quality of life and huge economic burdens on families and society. Traditional Chinese medicine (TCM) has “multi-target, multi component and multi-pathway”characteristics. Recent studies using animal and cell models demonstrated that the mechanism of OS progression was related to Notch, mitogen-activated protein kinase, Wnt/β-catenin, phosphatidylinositol 3-kinase/AKT, Hedgehog and nuclear factor-κB, transforming growth factor-β/Smad and signal transducer and activator of transcription pathways. TCM can exert anti-tumor effects by influencing biological processes such as cell proliferation, migration, invasion, apoptosis, and autophagy via interfering with the above signaling pathways. This review considers the roles of these signaling pathways in OS and summarizes the current research status of TCM interventions in the prevention and treatment of OS, with the aim of providing a reference for future studies of TCM treatments of OS and to provide new ideas for its clinical treatment.