Skin aging/photoaging is associated with altered the structure of collagen and elastin fibers, and increased activity of matrix metalloproteinases (MMP) and elastase. Nicotinamide and its derivatives, 2,6-dihydroxynicotinamide, 2,4,5,6-tetrahydroxynicotinamide, and 3-hydroxypicolinamide (collectively niacin derivatives) stimulate fibrillar collagen and heat shock proteins in dermal fibroblasts. The goal of this research was to extend the understanding of the anti-skin aging mechanism of these niacin derivatives through the stimulation of elastin (at the protein and promoter levels), fibrillin (1 and 2) in nonirradiated or ultraviolet (UVA) radiated dermal fibroblasts, and through the direct inhibition of MMP (1, 3, and 9) and elastase activities. UVA radiation stimulated elastin and inhibited fibrillin-1 and fibrillin-2 in dermal fibroblasts. The niacin derivatives significantly stimulated the expression of elastin (transcriptionally), fibrillin-1 and fibrillin-2 in nonirradiated and UVA radiated fibroblasts, and directly inhibited MMP or elastase activity. Overall, the niacin derivatives, more so nicotinamide and 2,6-dihydroxynicotinamide, have anti-skin aging potential through the stimulation of elastin and fibrillin, and the direct inhibition of the extracellular matrix proteolytic enzymes.