The applications of composite films in wound healing are immense, and the quest for suitable biomaterials drives research. Natural polymers lack mechanical strength; by cross-linking, their chemical nature can be changed through interlinking via intermolecular interactions rather than chemical bonds. This study explores the applications of cross-linked chitosan–polyvinyl alcohol–genipin films prepared using the solvent casting method. The cross-linked films were analyzed for their chemical structural changes, structural morphology, mechanical strength, and water retention capabilities. Comparative studies were performed with the un-crosslinked counterparts. Results indicated an increased tensile strength of 67.2% and improved water retention because of their compact structure. Further, Fourier-transform infrared spectroscopy confirmed that cross-linking occurred in the films, and scanning electron microscope micrographs showed that the films were uniform with a continuous morphology. Thereafter, an in vivo study was performed to assess the effectiveness of the films on wounds made on Albino Wistar rats. Histopathological analysis indicated quick fibroblast generation and angiogenesis using the cross-linked films, affirming their suitability for wound healing applications. [Display omitted] • Chitosan-PVA-Genipin cross-linked films were prepared using the solvent-casting method. • The c films were analyzed for chemical structural changes, structural morphology, mechanical strength, and water retention capacities. • The cross-linked films were assessed in-vivo for their wound healing properties on Albino Wistar rats. • Results confirm cross-linking and present excellent mechanical and water retention properties of the cross-linked films. • The films induced accelerated healing, quick fibroblast generation and angiogenesis, affirming their suitability for wound healing applications. [ABSTRACT FROM AUTHOR]