Introduction: Obesity is characterized as a low-grade inflammation that impairs physiological functions, including intestinal functioning and gut microbiota balance. Dietary polyphenols can be a strategy for obesity management, collaborating to preserve or recover gut health through antioxidant and anti-inflammatory actions, as well as modulators of the microbiota. This study describes a systematic review protocol to elucidate effects of polyphenols on intestinal health of pre-clinical models with diet induced obesity. AIM: Our aim is to evaluate evidence about polyphenols’ effects in the gut microbiota composition and diversity, parameters of the physical and molecular status of the gut barrier in obese models, additionally, understand the possible involved mechanisms. Methodology: A protocol was developed and published on PROSPERO (Registration No: CRD42021262445). Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols is used to outline the protocol. The articles will be selected according to the PICOS strategy (population, interventions, control, outcome, and study design) in the following databases: PubMed, Science Direct, Scopus, Web of Science, and EMBASE. Experimental studies performed on rats and mice with a control group that describes treatment with polyphenols (from food matrix or crude extracts or isolated compounds) at any frequency, time, and dose will be included. Two reviewers will, independently, select the papers, extract data, and evaluate the data quality. The Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool will be used to assess the risk of bias. Expected results:Results will be showed through of native synthesis and, if possible, a metanalysis will be conducted. The review produced with this protocol can show the scientific evidence level about polyphenols’ effects in intestinal health in obesity status. Abbreviations: CFU = colony-forming unit, MeSH = Medical Subject Headings, OTUs = Operational taxonomic units, PICOS = population, interventions, control, outcomes, and study design, PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses, PRISMA-P = Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols, PROSPERO = International Prospective Register of Systematic Reviews, SFCA = Short-chain fatty acids, SYRCLE = Systematic Review Center for Laboratory Animal Experimentation