INTRODUCTION: Intestinal barrier function is dependent on the structure and function of intestinal epithelial cells and paracellular pathway. The derangement of the intestinal barrier function can originate from conditions involving local and systemic chronic inflammation and metabolic diseases such as obesity and metabolic disorders. This study aims to describe a systematic review protocol investigating if obesity with or without metabolic syndrome is associated with an altered intestinal barrier function. METHODS AND ANALYSIS: This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. The databases to be searched are PubMed, Embase, Scopus, Science Direct and Web of Science. The systematic review will include original articles with adults and the elderly, who present obesity with or without metabolic syndrome, that address the intestinal barrier function. Two independent reviewers will perform study selection, data extraction and methodological quality assessment. Key information will be tabulated and a narrative synthesis will be conducted. The Grading of Recommendation, Assessment, Development and Evaluation framework will be used to assess the quality of evidence concerning the associations between intestinal barrier function and obesity with or without metabolic syndrome. The present protocol will assist in producing a systematic review that addresses if obesity with or without metabolic syndrome alters intestinal barrier function. ETHICS AND DISSEMINATION: No ethical statement will be required. The results will be disseminated through a peer-reviewed publication and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42020178658.