BackgroundAllergic diseases affect around 40% of the pediatric population worldwide. The coexistence of asthma, allergic rhinitis, eczema, and food allergy renders allergy treatment and prevention challenging. Infant feeding strategies recommend avoiding allergenic foods to prevent allergy development and anaphylaxis. However, recent evidence suggests that early consumption of food allergens during weaning in infants aged 4-6 months could result in food tolerance, thus reducing the risk of developing allergies.ObjectiveThe aim of this study is to systematically review and carry out a meta-analysis of evidence on the outcome of early food introduction for preventing childhood allergic diseases.MethodsWe will conduct a systematic review of interventions through a comprehensive search of various databases including PubMed, Embase, Scopus, CENTRAL, PsycINFO, CINAHL, and Google Scholar to identify potential studies. The search will be performed for any eligible articles from the earliest published articles up to the latest available studies in 2023. We will include randomized controlled trials (RCTs), cluster RCTs, non-RCTs, and other observational studies that assess the effect of early food introduction to prevent childhood allergic diseases.ResultsPrimary outcomes will include measures related to the effect of childhood allergic diseases (ie, asthma, allergic rhinitis, eczema, and food allergy). PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines will be followed for study selection. All data will be extracted using a standardized data extraction form and the quality of the studies will be assessed using the Cochrane Risk of Bias tool. Asummary of findingstable will be generated for the following outcomes: (1) total number of allergic diseases, (2) rate of sensitization, (3) total number of adverse events, (4) improvement of health-related quality of life, and (5) all-cause mortality. Descriptive and meta-analyses will be performed using a random-effects model in Review Manager (Cochrane). Heterogeneity among selected studies will be assessed using theI2statistic and explored through meta-regression and subgroup analyses. Data collection is expected to start in June 2023.ConclusionsThe results acquired from this study will contribute to the existing literature and harmonize recommendations for infant feeding with regard to the prevention of childhood allergic diseases.Trial RegistrationPROSPERO CRD42021256776; https://tinyurl.com/4j272y8aInternational Registered Report Identifier (IRRID)PRR1-10.2196/46816