Fermentation of red ginseng (RG) produces fermented red ginseng (FRG), thereby increasing the relative amount of downstream ginsenosides, including compound Y (CY), F2, Rh2, compound K (CK), compound O, protopanaxadiol (PPD), and protopanaxatriol (PPT). These downstream ginsenosides have beneficial pharmacological effects, and are easily absorbed by the human body. Based on these expectations, a randomized, single-dose, two-period, crossover clinical trial was planned to compare the pharmacokinetic characteristics of seven types (Rb1, CY, F2, CK, Rh2, PPD, and PPT) of ginsenoside components after FRG and RG administration. The safety and tolerability profiles were assessed in this clinical trial. Sixteen healthy Korean male subjects were administered 6 g of FRG or RG. All ginsenosides except Rb1 showed higher systemic exposure after FRG administration than after RG administration, based on comparisons of ginsenoside C_max and area under the concentration–time curve (AUC) between FRG and RG. CK, the main ginsenoside component produced during the fermentation process, had 69.23/74.53-fold higher C_max/AUC_last after administration of FRG than RG, and Rh2 had 20.27/18.47-fold higher C_max/AUC_last after administration of FRG than RG. In addition, CY and F2 were detected in FRG; however, all plasma concentrations of CY and F2, except in one subject, were below the lower limit of quantification in RG. There were no clinically significant findings with respect to clinical laboratory tests, blood pressures, or adverse events. Therefore, regular administration of FRG may exert better pharmacological effects than RG.