Betanin (BET) can reduce the side effects of potent anticancer drugs e.g. doxorubicin (DOX) on the normal tissues in co-administration with them because of the synergistic therapeutic effect and consequently the reduced required amount of anticancer agents. Despite interest in the use of BET, incomplete oral absorption and low stability of BET limit its application. Thus, in this study to overcome the restrictions of BET and providing the synergistic effect of DOX@BET, we designed a new pH-responsive nanocarrier via decoration of gelatin nanoparticles (GNPs) by (methoxy poly (ethylene glycol)-poly ((2-dimethylamino) ethyl methacrylate-co-itaconic acid) (PGNPs). DOX and BET were effectively loaded (the loading capacity of 20.5% and 16.25%, respectively) into the PGNPs and this nanoplatform exhibited the suitable small particle size (162 nm). Additionally, the triggered release ability of drugs was studied through the assessment of simulated physiological and tumor tissue environments and showed the controlled release of DOX and BET with adjusting the pH of environment. Moreover, the synergistic effect of DOX@BET loaded PGNPs decreased the cell viability amount of breast cancer cells (MCF-7) respect to the free form of DOX or BET which indicated that the developed smart nanocarrier will be a hopeful nanocarrier for cancer therapy.