The interest in the consumption of health-promoting foods has led to identifying derivatives of the wine industry as products to increase the functional properties of different foods or to design new functional foods. The main goal of this study is to characterize and valorize byproducts and wastes of Sicilian grapes as new sources of bioactive components, from the perspective of a circular economy and a biorefinery approach. In particular, this research investigated: 1. the total phenolic content and antioxidant activities and 2. the phenolic profiles of free and bound fractions of defatted grape seeds and red grape skins from Sicily. Defatted grape seeds (DGS) and red grape skins (RGSK) are rich in phenolic compounds. Twenty biophenols were found in the defatted seeds and red grape skins. Particularly interesting were the results obtained after basic hydrolysis, which allowed the release of biophenols from the matrix. The degreased grape seeds showed p-coumaric acid levels at 4641.65 µg g⁻¹, gallic acid at 2649.23 µg g⁻¹, and caffeic acid at 1474.13 µg g⁻¹, along with appreciable quantities of myricetin, epicatechin, and quercetin. As a sustainable approach, the reuse and the value added of the byproducts and wastes of grapes grown in Sicily is shown, which makes possible new applications in different fields, i.e., nutraceuticals.