Keloids are benign dermal fibrotic tumors arising during the wound healing process. The mechanisms of keloid formation and development still remain unknown, and no effective treatment is available. Resveratrol, a dietary compound, has anticancer properties and, from recent studies, it has been suggested that resveratrol may have an antifibrogenic effect on organs such as the liver and kidney. Based on this idea, we investigated its effect on the regulation of extracellular matrix expression, proliferation, and apoptosis of keloid fibroblasts. Type I collagen, α-smooth muscle actin, and heat shock protein 47 expression decreased in resveratrol-treated keloid fibroblasts in a dose-dependent manner. In addition, resveratrol diminished transforming growth factor-β1 production by keloid fibroblasts. We also demonstrated that it suppressed their proliferation and induced apoptosis of the fibroblasts. Conversely, resveratrol did not decrease type I collagen, α-smooth muscle actin, and heat shock protein 47 mRNA expression in normal skin fibroblasts and barely suppressed cell proliferation. Our data indicate that resveratrol may have an antifibrogenic effect on keloid fibroblasts without any adversely effects on normal skin fibroblasts, suggesting the potential application of resveratrol for the treatment of keloids.