Display omitted •Microwave-assisted extraction is used to extract polyphenols from white button mushrooms.•RSM was combined with different parameters at which extraction was carried out.•The study investigated optimal conditions for the extraction of bioactive compounds.•White button mushroom is a good source of polyphenols and antioxidants. Response surface methodology (RSM) was used to optimize the microwave-assisted extraction (MAE) of phenols from white button mushrooms (Agaricus bisporus). The total phenolic content (TPC), total flavonoid content (TFC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, and ferric reducing antioxidant power (FRAP) assays of white button mushrooms were optimized using three extraction parameters: ethanol concentration (10–90 %), extraction time (1–30 min), and solvent-to-solid ratio (5–20 mL of ethanol/water (80:20, v/v) solvent added to fixed amount of 0.2 g of sample for extraction). The ideal conditions for TPC were 58 % ethanol concentration, 16 min of extraction duration, and a solvent-to-solids ratio of 12.9 mL/0.2 g. 56 % ethanol concentration, an extraction period of 18 min, and a solvent-to-solid ratio of 12 mL/0.2 g were the ideal TFC conditions. Furthermore, the optimal conditions for maximum antioxidant activity also revealed the significant effect of independent variables. The experimental values of the responses were correlated with the predicted response values, which suggested the efficiency of MAE for extracting polyphenols from white button mushrooms. White button mushroom is an excellent antioxidant source, and conditions to extract phytochemicals have been optimized using RSM.