Cabernet Sauvignon grape juice and wine underwent in vitro digestion, resulting in a reduction of most phenolic compounds (10%–100% decline), notably impacting anthocyanins (82%–100% decline) due to pH variations. However, specific phenolics, including p–hydroxybenzoic, protocatechuic, vanillic, p-coumaric, gallic and syringic acids, and coumarin esculetin, increased in concentration (10%–120%). Grape juice and wine samples showed comparable polyphenolic profile during all phases of digestion. Antioxidant activity persisted, and inhibition of angiotensin-I converting enzyme was improved after the digestion process, likely because of increased concentrations of listed phenolic acids and esculetin. Digested grape juice displayed comparable or superior bioactivity to red wine, indicating it as a promising source of accessible grape polyphenols for a broader audience. Nevertheless, Caco-2 cell model metabolization experiments revealed that only 3 of 42 analyzed compounds passed to the basolateral compartment, emphasizing the significant impact of digestion on polyphenol bioactivity, suggesting potential yet unmeasurable and overlooked implications for human health. Display omitted •Digestion caused a decline in concentration of most phenolics except phenolic acids.•Amount of anthocyanins was mostly reduced during digestion.•Digestion preserved antioxidant activity of grape juice and wine.•Only 3 of 42 analyzed compounds passed to the basolateral compartment of Caco-2 cells.•Grape juice is valuable source of grape polyphenols for wider consumption than wine.