Polyurethane (PU) foam was combined with protein drug-loaded pH-sensitive alginate-bentonite hydrogel for wound dressings. Alginate is a linear copolymer composed of 1–4-linked β-D-mannuronic acid (M) and its c-5-epimer α-Lguluronic acid (G). The amount of (M) and (G) and their sequential distribution are varied depending on the alginate source. Soluble sodium alginate can become a hydrogel when cross-linked with divalent cations and has widespread applications in the food, drink, pharmaceutical and bioengineering industries. Recently, it has been also proposed as a biomaterial for drug delivery systems. Bentonites are the natural inorganic polymers consisting of a large proportion of expandable clay minerals with a three-layer structure such as montmorillonite, beidellite, nontronite, etc. They are important adjutants and supports for medical products, and they have many useful physicochemical, mechanical, and biological properties such as absence of toxicity, indifference to other raw materials, sorption, swelling, and complex formation properties. Alginate-bentonite hydrogels were prepared at concentration ratios of 10/0, 7/3, 5/5, 3/7. PU foams were prepared using hydrophilic polyols. We investigated the controlled release of a protein drug from PU foam combined with alginate-bentonite hydrogel at different pH values of 4.2, 5.2, 7.2, 8.2. The mechanical properties and cytotoxicity tests of this foam were also studied.