BackgroundIrritable bowel syndrome (IBS) is associated with various gastrointestinal and nongastrointestinal symptoms and reduced quality of life. A diet low in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) is one therapeutic option for IBS. Although the efficacy of the low FODMAP diet has been reported in several systematic reviews, the efficacy-effectiveness gap of the low FODMAP diet has not yet been assessed.ObjectiveThis systematic review aims to compare the efficacy of the low FODMAP diet from efficacy randomized controlled trials (RCTs) with the effectiveness of studies conducted in “real-world” settings.MethodsRCTs, prospective and retrospective cohort studies, and retrospective audits assessing the low FODMAP diet in adults with IBS will be searched in 4 databases: Embase, MEDLINE, CENTRAL, and CINAHL. Two independent reviewers will perform study selection, data extraction, and risk of bias assessment and assess selected quality aspects from the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) protocol. Outcomes assessed are stool frequency, stool consistency, abdominal pain, overall symptom scores, adequate symptom relief, IBS-specific quality of life, and diet adherence. Data will be summarized with forest plots without summary statistics, tables, and narrative descriptions.ResultsThe search, title and abstract screening, and full-text screening were completed in March 2021, and an updated search was done in May 2022. As of May 2023, data analysis is almost finished, and manuscript writing is in progress. Submission of the manuscript is expected by July 2023.ConclusionsThe findings of this systematic review will compare the efficacy of the low FODMAP diet for IBS found in RCTs to the diet’s real-world effectiveness.Trial RegistrationPROSPERO CRD42021278952; https://tinyurl.com/32jk43evInternational Registered Report Identifier (IRRID)DERR1-10.2196/41399