Large-fruited cranberry (Vaccinium macrocarpon Ait.) is a rich source of polyphenolic compounds, including anthocyanins, flavonols, and unique A-type proanthocyanidins, which exhibit strong antioxidant and health-promoting properties. Cranberry pomace, a by-product generated during juice and concentrate production, remains underutilized despite being abundant in dietary fiber and non-extractable polyphenols (NEPPs). In this study, cranberry pomace was characterized phytochemically and applied as a functional ingredient in biscuits at levels of 5%, 10%, and 15% substitution of wheat flour. Total polyphenol content (TPC) and antioxidant activity (ABTS•+, DPPH•) were significantly higher in pomace compared to whole fruit values reported in the literature, which can be attributed to the concentration of polymeric proanthocyanidins and flavonols in skins and seeds. Biscuits enriched with pomace exhibited a dose-dependent increase in TPC and antioxidant capacity, with the 15% variant showing up to 6-fold higher polyphenol content and over 30-fold higher ABTS•+ activity after in vitro digestion compared to control. Digestion also released NEPP bound to the fiber matrix, improving bioaccessibility. Moreover, extracts from digested biscuits reduced oxidative stress in Saccharomyces cerevisiae and inhibited COX-1, COX-2, and AChE activities, suggesting potential anti-inflammatory and neuroprotective effects. These findings highlight cranberry pomace as a sustainable, high-value ingredient for functional foods, aligning with circular economy strategies.