This study presents the characterization of hydrogels enriched with natural extracts of Withania somnifera (ashwagandha) and Lentinula edodes (shiitake) with respect to their potential biomedical applications. The obtained materials were evaluated in terms of swelling capacity, stability in different incubation media (Ringer’s solution, PBS, distilled water), antioxidant activity, as well as morphological and chemical changes after incubation. The results demonstrated that all hydrogels preserved their structural integrity over a 7-day period, while their properties depended on the type and ratio of incorporated extracts. Samples enriched with Lentinula edodes showed higher antioxidant activity but underwent more pronounced morphological changes, whereas hydrogels containing Withania somnifera were more structurally stable. FT-IR analysis confirmed the preservation of the polymeric backbone after incubation. Overall, the results indicate that the investigated hydrogels can serve as carriers of natural bioactive compounds, and their tunable composition offers promising potential for applications in tissue engineering and regenerative medicine.