Chronic wounds are a persistent clinical and public health challenge. Natural polyphenols such as curcumin and resveratrol, alongside mesenchymal stem cell (MSC) secretome, have demonstrated complementary anti-inflammatory, antioxidant, and pro-angiogenic properties with potential for wound healing. This study reports two complementary in vitro investigations evaluating the release profiles of curcumin and resveratrol from two polymeric platforms: poly(vinyl alcohol)/sodium alginate/carboxymethylcellulose films (Study 1) and an acrylate copolymer-based hydrogel incorporating MSC secretome (Study 2). UV-Vis spectrophotometric analysis confirmed analytical selectivity with no interference from excipients. In Study 1, films containing curcumin alone exhibited low structural stability and early disintegration in aqueous medium, whereas resveratrol-only films (2% w/w) demonstrated sustained and reproducible release profiles. Combined formulations showed that curcumin compromised polymer matrix integrity and reduced resveratrol release efficiency. In Study 2, resveratrol exhibited progressive and consistent release from the hydrogel, reaching 14.31 µg/mL (isolated control) and 12.60 µg/mL (combined with curcumin) at 120 min. Curcumin showed unsatisfactory release in both systems, attributed to its low aqueous solubility. These results support resveratrol-loaded polymeric matrices as promising sustained-release platforms for bioactive wound dressings and highlight the need for nanoencapsulation strategies to improve curcumin bioavailability.