Industrial waste management is a growing concern, and the valorization of by-products through circular economy approaches represents a sustainable solution. In this context, dextran–grape conjugates (PLG–GRAPE) were obtained via a grafting reaction of grape pomace extract and dextran under aqueous conditions. To compare the properties of the polymeric graft with those of the free extract, total polyphenol content was assessed using the Folin–Ciocalteu assay, along with stability and diffusion studies. In addition, in vitro safety evaluations, including Neutral Red Uptake, h-CLAT, and skin irritation tests were performed to assess the biocompatibility. To evaluate the antioxidant, anti-inflammatory, and anti-aging properties of PLG–GRAPE, in vitro efficacy assays were performed on keratinocyte and fibroblast cell lines and full-thickness reconstructed human tissues exposed to damaging agents, such as UV radiation and pollutants. The results showed that the technology preserved the phenolic and antioxidant activity of the extract, while improving diffusion and stability properties. As demonstrated by the results of the in vitro studies, a favorable biocompatibility profile was observed, in addition to a significant capacity to reduce oxidative stress and inflammation in aged cells, thus, attenuating cellular aging and senescence. In conclusion, the study suggests that PLG–GRAPE has potential as a bioactive ingredient for cosmetic and dermatological applications, offering a sustainable and effective approach to utilizing industrial waste products.