The aim of this study was to investigate the antihistamine activity of steam-exploded oak (Quercus variabilis) extract containing phenolic compounds. The antioxidant activity increased with residence time of the steam explosion process. The 50% EtOH extract had total phenolic compound content of 82.2 % and 46.2 mg GAE/g extract and vanillic acid, ferulic acid, and vanillin were identified. Treatment with 50% EtOH extract decreased the diameters of histamine-induced wheal and erythema responses in human volunteers. In patients with atopic dermatitis, topical administration of 50% EtOH extract led to significant diseases and improvement in terms of sleep disturbance, pruritus, xerosis, desire to scratch, and erythema. This study suggested that steam-exploded oak is rich in phenolic compounds with high antioxidant and antihistamine activities, and the extract may be a promising source of new antihistamine agents and pharmaceuticals.