The purpose of this investigation was (i) the development of a novel, green tertiary solvent system, composed of water, ethanol and glycerol, and (ii) the implementation of an organosolv treatment of red grape pomace (RGP) for the efficient production of polyphenol-containing extracts with enhanced antioxidant properties. The treatment developed was performed under mild acidic conditions, imparted by the addition of citric acid, and it was first evaluated on the basis of severity, establishing linear models that described the correlation between treatment performance and combined severity factors. To solicit treatment optimization, response surface methodology was implemented, considering solvent acidity and residence time as the treatment variables. The optimized treatment afforded maximum total polyphenol (166 ± 6 mg GAE g-1 DM), total pigment (4.4 ± 0.2 mg MvE g-1 DM) and total flavanol (31.5 mg CtE g-1 DM) yields and extracts with particularly enhanced antioxidant activity. This might be attributed to specific constituents with high antioxidant potency, such as catechin, determined in the extract using high-performance liquid chromatography. Thus, the treatment developed is proposed as a highly efficient process to generate RGP extracts enriched in polyphenolic compounds, with enhanced antioxidant activity. Such extracts might then be valorized as food additives, to provide antioxidant protection and/or pigmentation.