In this work, a preliminary experimental plan was set up to investigate the effect of an enzymatic pre-treatment (ET) of grape skins (GS) on the release of total phenols and antioxidant compounds in a next step of aqueous ethanol extraction and on the content of total dietary fibre (TDF) and water retention capacity (WRC) of the GS. Dried and milled GS were obtained from fermented pomace of different red grape cultivars: a mixture of San Giovese - Merlot (SGM) and Croatina (CRO). SGM-GS were micronized (250 µm), while CRO-GS were milled at particle size < 2 mm. A commercial food grade enzyme preparation (Viscozyme® L, by Novozyme Corp.), was used to carry out the ET at a 3 % enzyme load (w/w based on dry weight of GS), 24 °C, 4 h under stirring, at two different moisture levels (17 and 72 %). After the ET, a conventional solvent extraction with 60 % ethanol at a solid/solvent ratio (SSR) of 1/7 or 1/24 (for the 17 % and 72 % moisture level of the ET, respectively), at 40 °C and under stirring for 90' was conducted. The extracts were characterised for total free phenols (TP); total anthocyanins (TA) and antioxidant capacity (ABTS and FRAP assay) and compared with direct solvent extraction control treatments. For the micronized SGM-GS, the ET allowed for a slight but significant increase in TP and TA release only for the 1/24 SSR. For the coarser CRO-GS, the ET significantly increased the TP and TA release only for the 1/7 SSR, apparently compensating the limitation to mass transfer given by lower surface area, which could be exploited to reduce the energy cost of extensive GS milling. Almost the same trend was observed for the antioxidant capacity. Analysis of TDF revealed a significantly reduction of this parameter after ET confirming the enzyme action on the cell wall components.