Korean red ginseng (KRG, Panax ginseng C.A. Meyer) has traditionally been considered to harbor anti-allergic effects, however its action on atopic dermatitis (AD) is unclear. Therefore, we investigated the effect of KRG on AD using NC/Nga mice as an AD model. In addition, we examined the effect of aprepitant (substance P specific neurokinin receptor antagonist) on AD. The KRG extract and aprepitant were administered orally to NC/Nga mice. The efficacy of KRG and aprepitant was evaluated by assessing total clinical severity score, ear thickness, serum IgE level and histology. In addition, mRNA and protein expression were measured by real-time RT-PCR and immunohistochemistry, respectively. The KRG extract significantly reduced the total clinical severity score, ear thickness and the level of serum IgE in AD mouse model, whereas aprepitant reduced only the serum IgE level. KRG not only decreased TNF-α, IFN-γ and substance P but also reduced the infiltration of FOXP3+ regulatory T (Treg) cells and CD1a+ Langerhans cells in the lesions, whereas aprepitant decreased only substance P and the infiltration of Treg cells. These results suggest that KRG extract may be a potential therapeutic modality for AD and aprepitant could be used as adjunctive agent to control pruritus in AD.