Grape seeds and skin are by-products of wine making or juice making operations which are considered as a good source of bioactive compounds. In this study, the total phenolic content (TPC) from Vitis vinifera L. cv. Ahmar Bou-Amar seeds and skin was optimized by conventional solvent extraction (CSE) and microwave-assisted extraction (MAE) using response surface methodology (RSM), then a comparative study was carried out. The optimal conditions for seeds extracted by CSE were: 74.33% v/v of ethanol concentration, 65.23 mm extraction time, 0.1 g/70.86 ml solid/liquid ratio, and for those extracted by MAE were: 59.88 s irradiation time and 373.15W microwave power. The extract obtained under these conditions showed a TPC of 96.56 +/- 1.29 mg GAE/g and 73.15 +/- 0.20 mg GAE/g DW for CSE and MAE, respectively. Concerning skin, the optimal conditions for CSE were: 51.46% v/v of acetone concentration, 89.80 mm extraction time, 0.1 g/32.25 ml solid/liquid ratio and for MAE were: 113.74s irradiation time and 384.44W microwave power. The extract obtained under these conditions showed a TPC of 39.57 +/- 0.23 mg GAE/g and 54.84 +/- 0.41 mg GAE/g DW for CSE and MAE, respectively. The TPC of seeds extract obtained with MAE was 24% lower than that of the CSE extract; also, the antioxidant activity of CSE extract is better than that of MAE extract. While, the TPC of skin extract obtained with MAE was 28% higher than that of the CSE extract and the antioxidant capacity was significantly higher than that of the CSE extract. The results indicate that the extracts of cv. Ahmar Bou-Amar seeds and skin contain a high quantity of polyphenols; therefore, they can be considered as a good source of natural antioxidants.