Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disorder of the esophagus with rising prevalence. Dupilumab (DUPI), a monoclonal antibody that targets the interleukin-4 receptor α, has shown promise as a treatment option. We conducted a systematic review and network meta-analysis of randomized controlled trials searching the PubMed/Medline database, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials (CENTRAL), and the medRxiv preprint server up to 31 July 2024, assessing DUPI's efficacy and optimal dosing in the treatment of EoE. Finally, three randomized-controlled trials comprising 470 participants, including 102 children under 12 years of age, were included in the qualitative synthesis. Both high-exposure (HE-DUPI, 300 mg weekly) and low-exposure (LE-DUPI, 300 mg biweekly) regimens achieved significant histologic remission relative to placebo (OR = 26.88, 95% CI 11.98-60.29 for LE-DUPI; OR = 29.15, 95% CI 13.68-62.12 for HE-DUPI). Although overall adverse events were comparable between groups, HE-DUPI was associated with a notable increase in serious adverse events. These findings suggest that DUPI is effective in promoting histologic remission in EoE, with LE-DUPI emerging as a preferred option for balancing efficacy and safety. This study highlights the efficacy and safety profiles of different dosing regimens and pediatric groups. Further studies are warranted to explore long-term outcomes and identify patient subgroups that may derive the greatest benefit from DUPI therapy.