The objective of this study was to optimise the temperature (25–50 °C), time (1–24 h) and the solvent ratio (ethanol/water, 0–100%) for the phenolic compounds extraction of Ghure marc (unripe grape) using response surface methodology. The central composite design (CCD) generated satisfactory models for the optimisation of process variables. The results revealed that the ratio (X3) was the most significant parameter on total phenolic content (TPC) and antioxidant activity [% 2-diphenyl-1-picrylhydrazyl (DPPH)], and there was a significant correlation between TPC and antioxidant activity. The optimal conditions for temperature and time were 44.93 °C and 19.34 h, respectively, and the ratio of ethanol to water was 70.08, which verified with carrying out confirmatory experiments. Under this condition, TPC and %DPPH were 388.79 mg GAE per 100 g and 91.01, respectively. The results of this study revealed that the Ghure marc can be used as a low-cost source of natural antioxidant in food.