Ginsenosides, the major active ingredient of ginseng, show a variety of biomedical efficacies such as anti‐aging, anti‐oxidation and anti‐inflammatory activities. To understand the effects of 20‐O‐β‐D‐glucopyranosyl‐20 (S)‐protopanaxadiol (compound K), one of the major metabolites of ginsenosides on the skin, we assessed the expression level of approximately 100 transcripts in compound K‐treated HaCaT cells using cDNA microarray analysis. Compound K treatment induced differential expression of 40 genes, which have been reported to be involved in the organization of the structure of the extracellular matrix as well as defense responses in human skin cells. One of the most interesting findings is a two‐fold increase in hyaluronan synthase2 (HAS2) gene expression by compound K. We found that change in expression of HAS2 gene represents a specific response of HaCaT cells to compound K because hyaluronan synthase 1,3 was not changed by treatment with compound K. We also demonstrated that the compound K effectively induced hyaluronan synthesis in human skin cells and hairless mouse skin. A human clinical study indicated that topical application of compound K containing oil‐in‐water emulsion showed improvement of xerosis, wrinkle and fine lines in the aged skin. We concluded that compound K has anti‐aging effects by the induction of HAS2 gene expression and following hyaluronan synthase.