The aim of this work is to determine the in-vitro antioxidant and multi-drug resistant (MDR) reversal activity in resistant human ovarian cancer cell line (A2780 DX3) of Ruta Montana methanolic extract (RMME), a perennial aromatic herb originated from North Eastern Algeria belongs to the family Rutaceae. The preliminary phytochemical screening of the extract revealed the presence of flavonoids, tannins, saponins, coumarins and alkaloids. Quantitative determination of total phenolics and total flavonoids was carried out using colorimetric methods. The total phenolic content was found to be142.33 mg of gallic acid equivalent per gram of extract, while the content of flavonoid show a value of 23.093 mg of quercetin equivalent per gram of extract. The antioxidant activity was evaluated in vitro with the use of free radical scavenging activity method by DPPH assay, the result expressed in terms of IC50 was found to be 0.12 mg/ml. On the other hand, the synergistic property of RMME with doxorubicin was analysed on A2780 DX3 resistant cell line using MTT assay. The ability of various concentrations of RMME to reverse MDR to doxorubicin in A2780 DX3 cells was investigated by the MTT method in the presence of doxorubicin (7μM). The concentrations 10 and 40 mg/ml of RMME overcame the MDR with the reversal fold (RF) values of 2.01 and 4.56 respectively, but the concentrations 0.625 and 2.5 mg/ml were weakly active. Finally, from results it can be concluded that methanolic extract contains the most active secondary metabolites and is the potential candidate to isolate the active compounds responsible for the effects observed with R.montana.