Background: Artemisia scoparia has a widespread distribution and can be found commonly in Eurasia. In traditional Korean medicine, A. scoparia leaves and flowers are used against urethral complications, phlogistic problems, and in the treatment of hepatitis.BRMethods and Results: In the present study, the protective effect of santamarine isolated from A. scoparia was evaluated in Ultraviolet B (UVB)-damaged keratinocytes. Results showed that santamarine suppressed the production of reactive oxygen species in a concentration-dependent manner. Treating cells with santamarine decreased the generation of Matrix Metalloproteinase (MMP)-1 compared to that in cells treated with UVB alone. Additionally, the mRNA levels of MMP-1 and MMP-3 were remarkably lower in cells treated with santamarine than those in cells with UVB irradiation. Furthermore, upregulated protein levels of MMP-1, MMP-2, MMP-3, and MMP-9 following UVB exposure were ameliorated by the introduction of santamarine. Investigation of the mechanisms underlying the photoprotective effect of santamarine showed enhanced inhibition of MAPK/AP-1 signaling following santamarine treatment. The presence of santamarine also recovered the UVB-induced decrease in collagen amount.BRConclusions: Overall, these results demonstrated that santamarine has a potential protective effect against UVB-induced skin photoaging in keratinocytes in vitro. The mechanism behind this effect was suggested to be via suppression of MAPK/AP-1 signaling.