In the last few years, there has been an increasing tendency to use natural polymers for the fabrication of dressings for wound and burn management. Among them, alginate, a polysaccharide extracted primarily from marine algae, exhibits attractive properties being non-toxic, hydrophilic and biodegradable. The aim of this study was to characterize the in vitro biocompatibility and the efficacy of a composite polymeric material based on sodium alginate (NaAlg) and povidone iodine (PVPI) complex in a mouse model of wound healing. The developed material combines the excellent wound healing properties of alginates with the bactericidal and fungicidal properties of PVPI, providing a controlled antiseptic release. We demonstrated that the NaAlg/PVPI films are able to reduce the inflammatory response both in human foreskin fibroblasts after lipopolysaccharide (LPS) stimulus and in rodents after wound induction. Furthermore, the NaAlg/PVPI film-treated animals showed a significantly higher wound closure compared to untreated animals at each time point considered. Interestingly, the complete wound closure was achieved within 12 days only in the film-treated group, indicating that the full-thickness wounds healed more rapidly in these animals. The results demonstrate that the NaAlg/PVPI films are biocompatible and possess healing properties that accelerate the wound closure.