All acute and chronic wound management strategies have limitations. Therefore, there is an urgent need to develop new treatment options for wound healing. Hydrogels based on natural polymers offer advantages in wound management because they can reduce patients' pain, fight infection, and carry targeted drugs to speed up the healing process. In this study, we aimed to develop and investigate an alginate-grafted N-vinylcaprolactam-based matrix for a modified release of dexketoprofen (DEX), which is potentially useful in wound healing. Free radical polymerization and grafted techniques were used to prepare thermo-responsive hydrogels. The obtained hydrogels, unloaded hydrogel (HY) and dexketoprofen-loaded hydrogel (DEXHY), were characterized and analyzed. The concentration of DEX encapsulated in the polymer matrix was 4 mg/mL. The IC50 values found for the samples tested by us were 607.4 µg/mL for HY, 950.4 µg/mL for DEXHY, and 2239 µg/mL for DEX. The average value of cell viability (%) after the exposure of cells to DEXHY hydrogel was 75.4%. DEXHY exhibited a very good in vitro wound closure rate, given its ability to modify DEX release kinetics. The hydrogel developed in this study has shown considerable potential to facilitate and even accelerate wound healing, including surgical wounds, by inhibiting the overexpressed inflammation process.