Winemaking waste solids (WS, resulting from red grapes after fermentation and distillation to recover spirits) were subjected to various processing schemes for isolating fractions with antioxidant activity. The liquors entrapped in WS as received were separated by pressing and freeze-dried to yield a fraction with antioxidant activity (measured as DPPH radical scavenging capacity) comparable to those of synthetic antioxidants. A second approach based on the direct processing of raw WS in sulfuric acid medium under fixed operational conditions and further extraction of hydrolysis liquors with ethyl acetate enabled the isolation of a fraction with higher antioxidant ability at an improved yield. The most favorable approach started with a washing stage leading to liquors (which were directly freeze-dried to yield 1.20 g of extract/100 g of oven-dry WS and presented an EC50 of 0.41 g of extract/L) and washed solids, which were dried and subjected to hydrolytic processing (i) with water as a reactive in an autocatalyzed reaction (autohydrolysis) or (ii) with sulfuric acid solutions to give an ethyl acetate-soluble fraction with improved antioxidant properties (EC50 in the range of 0.18-0.40 g/L). Samples from washing liquors and processing of washed solids in aqueous medium were subjected to chromatographic fractionation and analysis to give isolates with remarkable antioxidant activity (with EC50 as low as 0.07 g/L) and to identify their major components.