Background: Graft-versus-host disease (GvHD) remains a challenging complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially in steroid-refractory cases. Dupilumab, a monoclonal antibody targeting IL-4Rα and inhibiting Th2-mediated inflammation, has recently emerged as a potential off-label treatment for cutaneous GvHD with atopic dermatitis (AD)-like features. However, comprehensive evidence on its use in this setting is limited. Methods: We conducted a systematic review following PRISMA guidelines (PROSPERO ID: CRD420250654155) to evaluate the efficacy and safety of dupilumab in cutaneous GvHD. Eligible studies included case reports and case series involving pediatric or adult patients treated with dupilumab after allo-HSCT. Data on patient characteristics, treatment regimens, clinical outcomes, and adverse events were extracted and analyzed descriptively. Individual patient data were pooled for a subset analysis. Results: Nine studies (6 case series, 3 case reports) encompassing 18 patients were included. Most patients (72%) were pediatric and affected by non-malignant disorders. Dupilumab was used after multiple prior therapies, with variable dosing regimens, especially in children. The overall response rate was 95%, with a complete response in 56% of cases, particularly in AD-like GvHD, while a partial response was obtained in two patients with sclerotic cutaneous chronic GvHD. Dupilumab was well tolerated, with no drug-related toxicities reported. Conclusions: Dupilumab appears to be a promising, well-tolerated option for steroid-refractory cutaneous GvHD, especially with AD-like features. Its use may reduce immunosuppressive burden and improve quality of life. These findings support the need for prospective studies and randomized trials to define its role and optimal use in GvHD management.