According to tradition, plants and herbs are potential cures for numerous illnesses. In recent decades, they have gained worldwide recognition as critical sources of new drugs, especially for cancer, and the focus on medicinal plant research has increased tremendously. Currently, research scientists attribute the occurrence of post-chemotherapy tumour exacerbation to the presence of cancer stem cells hidden in the bulk of the malignant tumour, forming a rare subpopulation that plays a major role in tumour re-initiation, progression and recurrence. There is increasing evidence of cancer stem cells in a wide array of tumours, and these cells could be the crucial target for future chemotherapy approaches. This review of the major plant-basedphy to chemicals with documented antagonistic activities against cancer stem cells, their molecular targets and the mechanisms involved, may serve as a guide for developing from the existing natural agents, more effective, and broader spectrum anti-cancer stem cell compounds with the potential for clinical application.