Studies have established the presence of a small subpopulation of cells within tumor cells, known as cancer stem cells (CSCs). These cells have evidently been the reason for metastasis, chemotherapy or radiotherapy resistance and tumor relapses in several types of cancers. CSCs are prone to epithelial-to-mesenchymal transition (EMT), resulting in aggressive tumors. They modulate various pathways of molecular signaling, including Wnt, Hedgehog and Notch, thus increasing the stem-like characteristics. Elevated expression of ATP binding cassette (ABC) transporter efflux pump as well as suppression of apoptosis has also increased anti-cancer drug resistance. Plants are known to possess bioactive compounds that can modulate these key regulators and hence eliminate CSCs. This review aims to report and summarize preclinical studies about the effects of phytocompounds on CSCs of various tumors. Furthermore, clinical trials carried out for some of these phytoconstituents are reported. Thus, selectively targeting CSCs with plant extracts and herbal preparations may be a promising remedial strategy for cancer.