The effects of a skin care system containing CoffeeBerry extract (CBE) are explored in a series of studies designed to evaluate its effects on fine lines and wrinkles, pigmentation, and gene expression. A 6-week pilot study was designed to assess the effects of twice-daily application of CBE 1% cream and CBE 0.1% cleanser in a study group of 30 participants with moderate photoaging. Ten of these participants were involved in a split-face arm that compared CBE with its vehicle. Blinded expert grading of photographs measured the global improvement of facial skin and also percent improvement of fine lines and wrinkles and pigmentation. In addition to the photographic analysis and evaluation undergone by all participants, biopsies were taken and sectioned from 4 participants in the split-face protocol in order to evaluate changes in collagen I, collagen IV, matrix metalloproteinase (MMP)-1, and IL-1β. The remaining 20 participants applied CBE cleanser and day and night creams to the entire face. In addition to this clinical study, an in vitro study was designed to examine the gene expression of extracellular matrix and adhesion-related proteins in cultured human skin fibroblasts exposed to 0.001% CBE once or twice a day for 72 hours. In the split-face arm, the degree of improvement from baseline at week 6 was greater on the facial side receiving the CBE system when compared with vehicle: 29% versus 8% (P≤.05), 24% versus 3% (P≤.05), and 15% versus 5% (P=.055) for global improvement, fine lines and wrinkles, and pigmentation, respectively. Biopsies showed the CBE system reduced MMP-1 and IL-1β relative to vehicle. In the full-face arm, global improvement and improvements in fine lines and wrinkles and pigmentation were observed at week 6 relative to baseline. The CBE creams were generally well tolerated. In the in vitro study, CBE up-regulated gene expression for 4 collagen structural proteins and down-regulated gene expression for 3 MMPs. CoffeeBerry extract appears to improve the appearance of photoaged skin and shows preliminary evidence of modulating aspects of the chemokine cascade involved in photoaging.