Despite of the recent advances in diagnostic and therapeutic approaches, cancer remains as the leading cause of death worldly with diverse causal factors regarding genes and environment. Invasion and metastasis, as one of the most important hallmarks for cancer, have restrained the successful clinical therapy and are the primary causes of death among cancer patients. So far, most chemotherapeutic drugs are not effective for metastatic cancer due to drug resistance and serious side effects. Therefore, it is urgently essential to develop more effective therapeutic methods. Owing to their diverse biological activities and low toxicity, naturally active compounds derived from Chinese medicines, as a complementary and alternative approach, are reported to promote the therapeutic index and provoked as an excellent source for candidates of anti-metastatic drugs. With the rapid development of molecular biology techniques, the molecular mechanisms of the effects of potential anti-invasive and metastatic Chinese medicines are gradually elucidated. This chapter reviews the potential anti-invasive and metastatic mechanisms of naturally active compounds from Chinese medicines, including suppression of EMT, proteases and cancer-induced angiogenesis, anoikis regulation of circulating tumor cells and regulation of miRNA-mediated gene expression, providing scientific evidence for clinically using Chinese medicines in the field of cancer therapy.