BACKGROUNDDeep eutectic solvents (DESs) have been tested as promising green solvents for the microwave‐assisted extraction of phenolic compounds from brewer's spent grain (BSG). Firstly, a preliminary screening with four different DESs was carried out in order to determine the most effective DES for recovering phenolic compounds (measured as total phenols) from BSG. Later, an experimental design using the DES found to be most effective in the preliminary screening was applied to optimize microwave‐assisted choline chloride (ChCl):glycerol extraction.RESULTSChCl:glycerol was the most effective DES tested in the preliminary screening to recover phenolic compounds (2.3 mg GA g−1 BSG), even more than methanol (80% v/v) as conventional solvent (1.2 mg GA g−1 BSG). On the other hand, using ChCl:glycerol as DES, a total phenols content of 2.89 mg GA g−1 BSG was obtained operating at 100 °C for 13.30 min and 37.46% (v/v) water in the DES, ferulic and coumaric acids being the most abundant. Moreover, a residual extracted solid with non‐disturbed structural carbohydrates was achieved, which could be successfully used in a biorefinery to obtain other products, such as biofuels or chemicals.CONCLUSIONSThe suitability of a novel and green extraction process based on DESs combined with microwave assistance for the recovery of phenolic compounds from BSG was demonstrated. © 2020 Society of Chemical Industry (SCI)