This study presents a pro-ecological approach for the efficient recovery of natural antioxidants from plant matrixes by optimizing the green microwave-assisted extraction (MAE) of bioactive compounds from Moringa oleifera Lam. leaves. A central composite design (CCD) coupled with response surface methodology (RSM) was employed to model and evaluate extraction performance as a function of eco-friendly process parameters: ethanol concentration (X1, % v/v), liquid-to-solid ratio (X2, mL g–1), and extraction time (X3, s). The predictive response models effectively mapped three independent targets: total phenolic content (TPC, Y1), total flavonoid content (TFC, Y2), and reducing sugar content (RSC, Y3). The individual optimal conditions (X1, X2, X3) to maximize yields were successfully determined to be (40% v/v, 50:1 mL g–1, 85 s) for TPC, (60% v/v, 50:1 mL g–1, 90 s) for TFC, and (20% v/v, 45:1 mL g–1, 100 s) for RSC. Under these respective parameters, experimental maximums reached 23.5 mg GAE/g, 20.8 mg RE/g, and 76.3 mg GE/g, closely validating the predictive simulations. Strong positive correlations were observed between antioxidant activity (AA) and both TPC (R2 = 0.78) and TFC (R2 = 0.73). These findings demonstrate that optimized MAE serves as an energy-saving and sustainable bioprocess for isolating high-value phytochemicals with minimal environmental impact.