Background: There remains unmet need for therapies for atopic dermatitis (AD) with favorable symptom control but less frequent dosing. Objective: To evaluate the benefits and safety of MG-K10, a humanized interleukin-4 receptor alpha-targeting antibody, in moderate-to-severe AD. Methods: In this multi-center, double-blind, randomized, phase II trial, 163 moderate-to-severe AD patients were randomized to receive 16-week treatment with MG-K10 150 mg every 4 weeks (Q4W), 300 mg every 2 weeks (Q2W) (n = 41), 300 mg Q4W (n = 41), or placebo (n = 40). Primary endpoint was the change in Eczema Area and Severity Index (EASI) scores from baseline to week 16. Results: The mean differences in EASI score at week 16 for the 300 mg Q4W, 300 mg Q2W, and 150 mg Q4W groups were -38.83% (95% confidence interval [CI]: -56.47% to -21.20%, P < 0.001), -27.06% (95% CI: -44.73% to -9.38%, P = 0.003), and -16.00% (95% CI: -33.66% to 1.67%, P = 0.076) compared with placebo group. The proportion of participants achieving EASI-75 at week 16 was 79.5%, 66.7%, 53.8%, and 28.9% in the 300 mg Q4W, 300 mg Q2W, 150 mg Q4W, and placebo groups. The incidence of adverse events was comparable across groups. Conclusion: MG-K10 demonstrates potential as a long-acting therapeutic option for managing symptoms of moderate-to-severe AD, with favorable safety profile. The preliminary efficacy and safety supported further validation of 300 mg Q4W in phase III trial.