Background: Topical applications of ligands of peroxisome proliferator-activated receptor-α (PPARα) improve skin barrier homeostasis as well as skin inflammation. Therefore, topical PPARαligands could improve clinical symptoms of atopic dermatitis (AD) patients. Objectives: We developed novel PPARαactivators from natural herbs such as Leonurussibiricus and Hydnocarpusanthelmintica and investigated their role using oxazolone (Ox) inducedAD murine model. Methods: Novel PPARα activators were topically applied on inflamed skin of Ox-AD mice. GW7647, a known PPARα activator, as a positive control and vehicle(PG:EtOH=7:3 v/v) as a negative control were also applied. The efficacy of novel PPARα activators was evaluated on gross feature and skin barrier functionin addition allergic inflammation. Results: Topical application of novel PPARα activators as well as GW7647 improved eczema lesion and skin barrier function such as basal transepidermal water loss (TEWL) and stratum corneum hydration, and reduced cutaneous allergic inflammation as well as serum IgE level. Conclusion: Novel PPARα activatorsextracted from natural herbs such as Leonurussibiricus and Hydnocarpusanthelmintica could be developed as potent topical therapeutic agents for AD patients