Introduction: Skin barrier dysfunction and ceramide deficiency are common in atopic dermatitis (AD). This study was conducted to evaluate the efficacy and safety of a novel moisturizer for the improvement of skin barrier function and AD-related symptoms. Methods: Ninety-four mild AD patients were enrolled in this prospective clinical trial. The subjects were randomly divided into two groups to receive different products: (1) the test moisturizer (ProAD) containing ceramide precursor, and (2) the control moisturizer. The target areas were measured for transepidermal water loss (TEWL) and hydration at baseline, week 2, and week 4. The disease severity and patients’ quality of life were also investigated. Results: After 4 weeks of application, the ProAD group showed significantly reduced TEWL, increased hydration, and improved disease severity. Both groups reported improved quality of life after applying moisturizers. No adverse effects were observed during the follow-up period. Conclusion: The ProAD moisturizer can be an alternative to improve skin barrier function, disease severity, and quality of life in patients with AD. It also has a favorable safety profile.