Curcuma has been used as an adjuvant treatment for osteosarcoma (OS) due to its anticancer compounds. However, the underlying mechanism remains unclear. Therefore, this study aimed to explore the mechanism of action of curcuma in the treatment of OS using network pharmacology and molecular docking. In this study, anticancer compounds were obtained from relevant literature, and curcuma-related targets and OS treatment targets were obtained from public databases. Protein‒protein interaction networks were constructed to screen out the hub genes using the STRING database and Cytoscape software. Cluster analysis of the protein modules was then performed using the Cytoscape MCODE plugin. Furthermore, Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed for common targets among curcuma targets and OS-related targets using the DAVID database. Finally, molecular docking was performed, and the results were verified by Auto dock Tool and PyMOL software. Our research identified 11 potential active compounds, 141 potential therapeutic targets and 14 hub genes for curcuma. AKT1, TNF, STAT3, EGFR, and HSP90AA1 were the key targets closely related to the PI3K/Akt signaling pathways, HIF-1 signaling pathways, ErbB signaling pathways, and FOXO signaling pathways, which are involved in angiogenesis, cancer cell proliferation, metastasis, invasion, and chemotherapy resistance in the microenvironment of OS. Molecular docking suggested that the core compound had a strong affinity for key targets, with a binding energy of less than – 5 kJ/mol. The study showed that curcuma-mediated treatment of OS was a complex process involving multiple compounds, targets, and pathways. This study will enhance the understanding of how curcuma affects the proliferation and invasion of OS cells and reveal the potential molecular mechanism underlying the effect of curcuma on OS lung metastasis and chemotherapy resistance.