Background: Korean ginseng (Panax ginseng Meyer) is a traditional herbal medicine used worldwide today. Ginsenoside Rd (Rd), one of its main ginsenosides, has been ascertained to have various pharmacological efficacies including neuroprotective and anti-inflammatory activities. Objectives: This work assesses the antioxidant and protective potentials of Rd against ultraviolet (UV)-B-induced skin photooxidative stress in HaCaT keratinocytes. Materials and Methods: Cell viability was detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Intracellular reactive oxygen species (ROS) were measured using dichlorodihydrofluorescein diacetate. Promatrix metalloproteinase-2 (proMMP-2) activity and protein were detected using gelatin zymography and western analysis. Total glutathione (GSH) content and total superoxide dismutase (SOD) activity were spectrophotometrically determined. Results: Rd, at varying concentrations non-toxic to HaCaT keratinocytes, attenuated the UV-B-induced ROS generation. Rd at 5, 12, and 30 μM attenuated the UV-B-induced proMMP-2 gelatinolytic activities to 59.3% ± 9.5%, 41.3% ± 9.5%, and 13.1% ± 8.9%, respectively, of those of the non-treated control cells. It could also diminish the UV-B-induced proMMP-2 protein levels. Rd at 5, 12, and 30 μM augmented the UV-B-reduced total SOD activities to 1.6 ± 0.2-, 2.4 ± 0.3-, and 3.2 ± 0.2-fold of those of the non-treated control cells, respectively. Rd could up-regulate the UV-B-reduced total GSH. Conclusion: Rd has counteracting properties against elevated ROS and proMMP-2 and attenuated GSH and SOD under UV-B irradiation, implying that it possesses a protective activity against photoaging possibly through up-regulating antioxidant components. These findings suggest that Rd can be considered as a novel natural resource for anti-photoaging functional cosmetics.