Background: Patients with atopic dermatitis (AD) are vulnerable to xerosis due to impaired skin barrier function, which makes moisturizing essential. Recently, zinc-alpha-2 glycoprotein (ZAG) has appeared to modulate the skin barrier function in AD, and has been proposed as a potential therapeutic molecule in AD. Objective: This study aimed to evaluate the effects of a ZAG-containing moisturizer on restoration of the skin barrier and clinical improvement of AD. Methods: In this randomized, double-blind study, 42 patients (average age, 26.5 years) with mild-to-moderate AD were enrolled. The subjects were divided into two groups, ZAG-containing moisturizer or control, in which the intervention or control were applied twice a day for 4 weeks. The primary outcome was a change in the eczema area and severity index (EASI) after 4 weeks, and the secondary outcome included the transepidermal water loss (TEWL), corneometer, visual assessment score (VAS) for pruritus and sleep disturbance, and investigator’s global assessment (IGA). Results: ZAG-containing moisturizer was well-tolerated, with a significant decrease in the EASI score compared to the control group after 4 weeks of application (p＜0.05). As objective assessments of skin barrier function, TEWL also showed a significant, rapid decrease in the ZAG group compared to the control group after 2 weeks of application (p＜0.05). A significant improvement in AD symptoms was observed at 4 weeks, such as the VAS score for pruritus and sleep disturbance, and IGA. Conclusion: The moisturizer containing ZAG (By the doctor Ato repair cream^Ⓡ, Whitecospharm, Korea) effectively restored the function of the skin barrier, which led to a relief in the signs and symptoms of AD. (Korean J Dermatol 2020;58(9):575∼582)