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Central composite design of response surface methodology (RSM) was employed to optimize the extraction time (X ₁ : 99.5–290.5 min) and temperature (X ₂ : 30.1–54.9 °C) of Schizophyllum commune aqueous extract with high antioxidant activities and total phenolic content (TPC). Results indicated that the data were adequately fitted into four second-order polynomial models. The extraction time and temperature were found to have significant linear, quadratic and interaction effects on antioxidant activities and TPC. The optimal extraction time and temperature were: 290.5 min and 35.7 °C (DPPH^• scavenging ability); 180.7 min and 41.7 °C (ABTS^•+ inhibition ability); 185.2 min and 42.4 °C (ferric reducing antioxidant power, FRAP); 290.5 min and 40.3 °C (TPC). These optimum conditions yielded 85.10%; 94.31%; 0.74 mM Fe²⁺ equivalent/100 g; 635 …