Tumor metastasis is one of the worst prognostic features of cancer. Although metastasis is a major cause of cancer-related deaths, an effective treatment has not yet been established. Here, we explore the antitumor effects of GO-Y030, a curcumin analog, via various mechanisms using a mouse model. GO-Y030 treatment of B16-F10 melanoma cells inhibited TGF-β expression and glycolysis. The invasion assay results showed almost complete invasion inhibition following GO-Y030 treatment. Mouse experiments demonstrated that GO-Y030 administration inhibited lung tumor metastasis without affecting vascular endothelial cells. Consistent with this result, GO-Y030 treatment led to the downregulation of MMP2 and VEGFα, inhibiting tumor invasion and metastasis. The silencing of eIF4B, a downstream molecule of S6, attenuated MMP2 expression. Our study demonstrates the novel efficacy of GO-Y030 in inhibiting tumor metastasis by regulating metastasis-associated gene expression via inhibiting dual access, glycolytic and TGF-β pathways.