Abstract: P-glycoprotein (P-gp) is the first transporter that is found to be associated with the sensitivity of cells to chemotherapeutic drugs. The main function of P-gp is to exclude exogenous substances from cells to prevent the body from absorbing harmful substances. Therefore, it is one of the self-defense and protection mechanisms under the physiological state of the body. However, this defense mechanism of P-gp protein also leads to decrease in the concentration of some drug molecules in cells, leading to multidrug resistance. The multidrug resistance of cells is one of the main reasons that leads to the failure of chemotherapy. Therefore, inhibiting the efflux function of P-gp is one of the effective methods to reduce or even reverse multidrug resistance of cells. Quercitrin was a kind of flavonoid monomer compound with low biological toxicity, good water solubility, and weak P-gp inhibitory activity. In order to enhance the P-gp inhibitory activity of Quercitrin, we synthesized Quercitrin metal complexes Cu-Quercitrin and Zn-Quercitrin, and their P-gp inhibitory activities were investigated at the cellular level. Cu-Quercitrin could increase the accumulation of rhodamine 123 and doxorubicin in MCF-7/ADR cells, and improve the cytotoxicity of doxorubicin. In fact, the effect of Cu-Quercitrin was significantly better than that of P-gp inhibitor verapamil. In contrast, Cu-Quercitrin had no effect on the accumulation of rhodamine 123 and doxorubicin in normal MCF-7 cells, suggesting that Cu-Quercitrin could inhibit the transport function of P-gp. Compared with the Cu-Quercitrin, Zn-Quercitrin had no significant effect on the accumulation of P-gp substrates rhodamine 123 and doxorubicin in drug-resistance MCF-7/ADR cells. Further studies showed that Cu-Quercitrin had no effect on the expression of P-gp, but reduced the content of adenosine triphosphate（ATP）in drug-resistant cells. Therefore, Cu-Quercitrin increased the accumulation of anti-cancer drugs in drug-resistant cells by reducing the content of ATP and inhibiting the transport function of P-gp, which was expected to alleviate the multi-drug resistance of cells mediated by P-gp. This study indicated that Quercitrin metal complexes, Cu-Quercitrin, could be a novel P-gp inhibitor. Meanwhile, metal complexes with diverse structures and abundant ligands were expected to be candidate compounds for effective P-gp inhibitors.