Grape pomace, the solid residue from winemaking, is a rich source of polyphenolic compounds with significant antioxidant properties. However, the efficient extraction of these valuable compounds remains a challenge. This study focuses on optimizing the conditions for the enzyme-assisted extraction of polyphenolic compounds from red grape pomace using cellulase, hemicellulase, and pectinase. The key variables investigated in this study were enzyme concentration, extraction time, and solid/liquid ratio. The results highlight the importance of selecting enzymes based on target compounds, as different enzymes were found to be more effective for specific phenolic fractions. Hemicellulase was most effective for phenolic acids, cellulase for catechins, and pectinase for anthocyanins. Enzyme-assisted extraction significantly increased the yield of phenolic compounds and resulted in higher total phenolic content and antioxidant activity compared to control samples treated with solid/liquid extraction without enzyme addition. These findings confirm that enzyme-assisted extraction is a promising approach for enhancing the recovery of polyphenolic compounds from grape pomace.