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Pumpkin (Cucurbita pepo L.) is a valuable vegetable with a high content of bioactive compounds. The present study aims to optimize the microwave-assisted extraction (MAE) parameters to achieve the highest yield of total phenolic content (TPC) from its pulp (PPU) and peel (PPE). Response surface methodology (RSM) in conjunction with central composite design was used. The factors considered were (i) ethanol concentration, (ii) microwave power level, (iii), irradiation time and (iv) solid to liquid ratio. The models obtained produced a satisfactory fit to the data regarding to TP extraction with desirabilities of 0.99 and 0.83, for PPU and PPE, respectively. The optimum conditions for their extraction were found to be ethanol concentration 60%, microwave power 300 W, extraction time 138.67s and a solid-to-liquid ratio 1/30 g/mL for PPU. And for PPE, they were ethanol concentration of 46.42%, microwave power of 100 W, extraction time of 180 s and a solid-to-liquid ratio of 1/36.33 g/mL. Under these optimized conditions, the experimental maximum yields of TPC were 795.41 ± 20.21 and 548.09 ± 13.68 mg GAE/100 g dry weight, respectively for PPU and PPE which was in close agreement with predicted values, thus indicating the suitability of the developed models. The antioxidant activity of the optimized extracts was determined using DPPH· and ABTS·+ radicals scavenging, ferric reducing power (FRAP) and total antioxidant activity (TAA). In the entire tests, PPU extract exhibited the best capacities with IC50 of 1324.45 ± 16.57, 1992.85 ± 34.55, 476.51 ± 1.63 and 480.67 ± 10.50 µg/mL in DPPH, ABTS, FRAP and TAA assays, respectively. Nevertheless, both optimized extracts revealed a moderate antimicrobial effect. According to FT-IR analysis, all found functional groups support the occurrence of phenolic acids and flavonoid compounds in the optimized extracts. The study revealed the effectiveness of MAE in enhancing the phenolic yield of PPU and PPE in a reduced time and lower solvent consuming. [ABSTRACT FROM AUTHOR]