In this study, nanocomposite collagen scaffolds incorporating gold nanoparticles (AuNPs) were prepared for wound healing applications. Initially, dose (<20ppm) and size (>20nm) of AuNPs that were not cytotoxic on HaCat keratinocytes and 3T3 fibroblasts were determined. Both collagen sponges and AuNP-incorporated nanocomposites (CS-Au) were cross-linked with glutaraldehyde (CS-X and CS-AuX). Incorporation of AuNPs into cross-linked scaffolds enhanced their stability against enzymatic degradation and increased the tensile strength. Hydrolytic degradation of CS-Au group was also less than CS after seven days. Upon confirming in vitro biocompatibility of the scaffolds with cytotoxicity assays, cell attachment and proliferation tests and the in vivo efficacy for healing of full-thickness skin wounds were investigated by applying CS-X, CS-AuX or a commercial product (Matriderm (R)) onto defect sites and covering with Ioban (R) drapes. Defects were covered only with drapes for untreated control group. The wound areas were examined with histopathological and biomechanical tests after 14 days of operation. CS-AuX group was superior to untreated control and Matriderm (R); it suppressed the inflammation while significantly promoting granulation tissue formation. Inflammatory reaction against CS-AuX was milder than CS-X. Neovascularization was also higher in CS-AuX than other groups, though the result was not significant. Wound closure in CS-X (76%), CS-AuX (69%), and Matriderm (R) (65%) were better than untreated control (45%). CS-AuX group had the highest tensile strength (significantly higher than Matriderm (R)) and modulus (significantly higher than Matriderm (R) and CS-X), indicating a faster course of dermal healing. Further studies are also needed to investigate whether higher loading of AuNPs affects these results positively in a statistically meaningful manner. Overall, their contribution to the enhancement of degradation profiles and mechanical properties, their excellent invitro biocompatibility, and tendency to accelerate wound healing are encouraging the use of AuNPs in collagen sponges as potent skin substitutes in the future.