This study was undertaken to investigate the inhibitory effects of triterpenoid compound oleanolic acid and its synthetic derivatives on osteosarcoma cells in order to identify new therapeutic candidates for the treatment of this disease. We used the 3-(4,5-dimethyl-2 thiazolyl)-2,5-diphenyl tetrazolium bromide assay to assess the effect of oleanolic acid compounds on the proliferation of osteosarcoma cells. The effect of dextrose-oleanolic acid (the most potent oleanolic acid derivative) on apoptosis of osteosarcoma cells was evaluated using the Annexin-V method. The cell cycle of dextrose-oleanolic acid-treated cells was examined by flow cytometry, and the in vivo effects of dextrose-oleanolic acid were evaluated in a mouse osteosarcoma model. Oleanolic acid compounds had an overall inhibitory effect on the proliferation of osteosarcoma cells. Our in vitro data showed that the dextrose-oleanolic acid derivative brought about maximal inhibition of proliferation of osteosarcoma cells while inducing apoptosis. It could also inhibit the growth of osteosarcoma and decreased the rate of lung metastasis in vivo. Of the oleanolic acid derivatives, dextrose-oleanolic acid exhibited the most potent anti-osteosarcoma activity; it may represent a new frontier in the treatment of osteosarcoma.