Developing new approaches to improve the swelling, degradation rate, and mechanical properties of alginate hydrogels without compromising their biocompatibility for biomedical applications represents a potential area of research. In this work, the generation of interpenetrated networks (IPN) comprised from alginate–polyurethane in an aqueous medium is proposed to design hydrogels with tailored properties for biomedical applications. Aqueous polyurethane (PU) dispersions can crosslink and interpenetrate alginate chains, forming amide bonds that allow the structure and water absorption capacity of these novel hydrogels to be regulated. In this sense, this work focuses on studying the relation of the PU concentration on the properties of these hydrogels. The results indicate that the crosslinking of the alginate with PU generates IPN hydrogels with a crystalline structure characterized by a homogeneous smooth surface with high capacity to absorb water, tailoring the degradation rate, thermal decomposition, and storage module, not altering the native biocompatibility of alginate, providing character to inhibit the growth of E. coli and increasing also its hemocompatibility. The IPN hydrogels that include 20 wt.% of PU exhibit a reticulation index of 46 ± 4%, swelling capacity of 545 ± 13% at 7 days of incubation at physiological pH, resistance to both acidic and neutral hydrolytic degradation, mechanical improvement of 91 ± 1%, and no cytotoxicity for monocytes and fibroblasts growing for up to 72 h of incubation. These results indicate that these novel hydrogels can be used for successful biomedical applications in the design of wound healing dressings.