Cancer cells demonstrate multiple drug resistance phenotype frequently after chemotherapy. The resistance of cancer cells to various chemotherapeutic agents is defined as multiple drug resistance. The purpose of this study is to investigate the potential reversal effects of active agents, that are found high amount in plants, on resistant MCF-7 cell lines. The effects of potential MDR modulators combined with anticancer drugs were also evaluated. Flow cytometry, fluorescence microscopy and checkerboard combination assays were performed to study the reversal of drug resistance and for investigation of the antiproliferative effects of the combination of anticancer drugs with the modulators. Paclitaxel and potential MDR modulators (verapamil, saikosaponin A, D and isoquercitrin) were applied to the sublines in combination. Fluorescence accumulation levels and fractional inhibitory indices show that saikosaponin A and D are effective MDR reversal agents that may be used together with paclitaxel in drug resistant mammary carcinoma subline. In conclusion this report represents saikosaponin A and D from natural resources are valuable reagents that may improve the success of chemotherapy.