Agro-industrial byproducts represent a serious environmental problem and the industries producing these residual materials have incurred expenses for their proper disposal and generally increase the pollution due to the high content of organic substances and might represent legal problems. However, the residues such as grape wastes are potential source of phenolic compounds which are widely known for their high antioxidant activity. Bioprocesses such as enzyme technology represent an alternative for production of those bioactive compounds from agro-industrial byproducts. In this study, different types of commercial enzymes such as Celluclast® 1.5 L, Pectinex® Ultra and Novoferm® were used to release phenolic compounds from grape wastes. The hydrolysates were analyzed in their total phenolic compounds and antioxidant activity with Folin–Ciocaletu test and DPPH· radical-scavenging assay, respectively. A good correlation was obtained between antioxidant activity and phenolics released. The highest antioxidant activities registered were 86.8 ± 0.81, 82.9 ± 0.31 and 90 ± 0.37 % at 12 h for Celluclast® 1.5 L, Pectinex® Ultra and Novoferm®, respectively. Novoferm® had the strongest effect on phenolic release from grape waste, followed by Pectinex® Ultra and Celluclast® 1.5 L. High performance liquid chromatography–electrospray–mass spectrometry clearly revealed that the increment of antioxidant activity is associated with the release of O-coumaric acid.