BACKGROUND Scientific research continues to develop more efficacious drugs to treat and cure cancer, the dreadful disease threatening the human race. Chemotherapy is an essential means in cancer therapy, however, plant drugs having pharmacological safety, can be used alone or as additions to current chemotherapeutic agents to enhance therapeutic efficacy and minimize chemotherapyinduced adverse effects. OBJECTIVE A combination therapy where the synergistic effect on multiple targets is possible has gained significance because a one-drug one-target approach fails to yield the desired therapeutic effect. Therefore, a detailed description of important plant polyphenolic compounds with anticancer activity and their role in potentiating chemotherapeutic efficiency of existing anticancer drugs is provided in this review. Systematically screening combinations of active pharmaceutical ingredients for potential synergy with plant compounds may be especially valuable in cancer therapy. METHODS We extensively have gone through reviews and research articles available in the literature. We made use of databases such as Google Scholar, Research Gate, PubMed, Science Direct, etc. The following keywords were used in our literature search: "Chemotherapy, drug development, cancer drugs, plant-derived polyphenolics, synergistic studies, combination therapy, diagnosis and genetics." CONCLUSIONS Systematic research studies on screening combinations of plant phytochemicals with potential chemotherapeutic pharmaceuticals shed light on their synergistic effects, mechanisms of actions paving the way to develop more efficient anticancer therapeutics to treat and cure the cancer menace, to nullify chemotherapy-induced adverse effects and our review substantially contributes in this direction.