In this study, our findings indicated that triphala was an antioxidant-rich herbal formulation containing polyphenols such as naringin, quercetin, homoorientin, Isorhamnetin, hypaconitine, and acaciin. Triphala (MET) exhibited dose-dependent antiproliferative properties in cancer stem cells (HCCSC) and cancer cells (HCT116) and proapoptotic properties in HCCSCs independent of p53 status of the cells. Furthermore, MET inhibited HCCSCs colony formation (stemness). MET suppressed proliferation/stemness might involve interplay of c-Myc/cyclin D1 signaling. Apoptosis induction by triphala was via the mitochondrial apoptotic signaling characterized by elevated Bax/Bcl-2 ratio. These results indicate that triphala (MET) may serve as an effective chemopreventive agent against colon cancer.