Microwave-assisted direct liquefaction of solid digestate was carried out in polyethylene glycol and glycerol employing sulfuric acid as catalyst, in order to convert it into a biofuel. Response Surface Methodology (RSM) coupled with Box-Behnken Design (BBD) with a total of 15 individual experiments was used to optimize the conditions of three independent variables (temperature, reaction time and solvent-to-biomass ratio) related to the bio-oil yield, the higher heating value (HHV) of bio-oil and the energy use of microwave treatment. Desirability function was employed to determine the optimal reaction conditions of the liquefaction process. The results showed that at the optimal conditions the bio-oil yield, the HHV of bio-oil and energy use were respectively 59.38%, 28.48 MJ/kg, and 115.93 Wh. The predicted responses showed a good compliance to the obtained experimental data. The optimized bio-oil was further characterized using FTIR analysis while the properties of the solid digestate and the liquefaction residue were analyzed by means of SEM analysis.