Background Ruxolitinib is a JAK1/2 inhibitor, which inhibits the signal transduction of interferon-gamma, a cytokine implicated in the pathogenesis of atopic dermatitis (AD). In this before-after single group phase IIA pilot study, we investigated the efficacy of topical nanoliposomal ruxolitinib phosphate (RuxoLip) emulgel in mild AD. Methods Clinical evaluation was conducted on 10 patients with mild AD. The efficacy of the product as well as patient satisfaction was evaluated by local scoring atopic dermatitis (SCORAD) of AD. In addition, trans-epidermal water loss (TEWL), stratum corneum (SC) hydration, sebum, erythema, melanin content, and ultrasonographic parameters were measured before, and two and four weeks after treatment. Results Four weeks of treatment reduced SCORAD, itching, and burning (p = .001, .001, and .001, respectively) and increased hydration, sebum, and epidermal density (p = .001, .018, and .037, respectively). SCORAD and other skin biophysical parameters improved within two weeks of treatment and then were in plateau for up to four weeks. Conclusions The topical ruxolitinib emulgel has good short-term efficacy and tolerability.