In this study, the potential value of dried grape pomace (whole, seed, and skin) obtained from Fetească Neagră (FN) and Tămâioasă Românească (TR) as a source of secondary metabolites was evaluated following hydroethanolic extraction. The total polyphenol, flavonoid, and anthocyanin contents of FN and TR extracts have been determined, along with their antioxidant and antimicrobial activities. The investigation of seeds and the whole pomace FN extracts revealed higher levels of polyphenol, flavonoid, and anthocyanin content in comparison to those extracted from TR. Fifteen polyphenolic compounds were identified through ultra-high-performance liquid chromatography (UHPLC) analysis. The most abundant concentrations of catechin and epicatechin were detected in seed and whole pomace extracts derived from both Romanian grape varieties. The antioxidant activity was higher in the whole pomace and skin extracts derived from FN than those derived from TR. The antimicrobial evaluation demonstrated that 15 out of 18 reference pathogenic bacteria exhibited low MIC and MBC values, indicating a strong antibacterial activity of FN and TR extracts. No anti-Candida activity was observed. It can be reasonably deduced that the Fetească Neagră and Tămâioasă Românească by-products represent a sustainable resource for the development of new functional ingredients for the pharmaceutical and food industries, in alignment with the principles of the circular bioeconomy.