Tiopronin (N-(2-mercaptopropionyl)glycine)-protected gold nanoparticles (TPAu) were cross-linked to collagen via EDC (1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide) coupling. On average, each TPAu forms eight amide bonds with collagen lysine moieties. The resulting gels were studied with environmental SEM, TEM, micro-DSC, and TNBS assay. The porous structure of collagen was significantly altered by cross-linking, resulting in the reduction of the pore size from ca. 140 to <1 microm depending on the concentration of nanoparticles. The collagenase biodegradation assay showed improved stability of cross-linked material. The cell viability assay, CellTiter96, indicates that the gold nanoparticles are not toxic at the concentrations used in gel synthesis. This new material has potential for the delivery of small molecule drugs as well as Au nanoparticles for photothermal therapies, imaging, and cell targeting.