Colorectal cancer (CRC) is the third most common cancer, and is associated with a high percentage of cancer-related death globally. Furthermore, the success rate of therapeutic treatment for CRC patients mainly depends on the status of metastasis. Therefore, novel drugs or therapeutic techniques should be discovered for the treatment of metastatic CRC. In this study, we selected Astaxanthin (AXT), one of the most common carotenoids, as a novel metastasis inhibitor through high-throughput drug screening based on invadopodia staining, and confirmed the anti-migratory and anti-invasive activity of AXT. We demonstrated that AXT increases miR-29a-3p and miR-200a expression, and thereby suppresses the expression of MMP2 and ZEB1, respectively. As a result, AXT represses the epithelial-mesenchymal transition (EMT) of CRC cells. Through the mechanistic study, we identified that AXT shows anti-metastatic activity through the transcriptional repression of MYC transcription factor. Finally, we also confirmed that AXT suppresses the in vivo metastatic capacity of colon cancer cell using mouse model. Collectively, we uncovered the novel function of AXT in the inhibition of EMT and invadopodia formation, implicating the novel therapeutic potential for AXT in metastatic CRC patients.