This work aims at studying the optimization of microwave-assisted extraction (MAE) and pressurized liquid extraction (PLE) by multi-response surface methodology (RSM) to test their efficiency towards the extraction of phenolic compounds from Moringa oleifera (M. oleifera) leaves. The extraction yield, total phenolic content (TPC), total flavonoid content (TF), DPPH scavenging method and trolox equivalent antioxidant capacity (TEAC) assay were considered as response variables while effects of extraction time, percentage of ethanol, and temperature were studied. Extraction time of 20min, 42% ethanol and 158 degrees C were the MAE optimum conditions for achieving extraction yield of 26 +/- 2%, EC50 15 +/- 2 mu g/mL, 16 +/- 1 Eq Trolox/100 g dry leaf, 5.2 +/- 0.5 mg Eq quercetin/g dry leaf, and 86 +/- 4 mg GAE/g dry leaf. Regarding PLE, the optimum conditions that allowed extraction yield of 56 +/- 2%, EC50 21 +/- 3 mu g/mL, 12 +/- 2 mmol Eq Trolox/100 g dry leaf, 6.5 +/- 0.2 mg Eq quercetin/g dry leaf, and 59 +/- 6mg GAE/g dry leaf were 128 degrees C, 35% of ethanol, and 20 min. PLE enabled the extraction of phenolic compounds with a higher number of hydroxyl-type substituents such as kaempferol diglycoside and its acetyl derivatives and those that are sensitive to high temperatures (glucosinolates or amino acids) while MAE allowed better recoveries of kaempferol, quercetin, and their glucosides derivatives.