There is a growing body of evidence implicating the gut ‘microbiome’ role in overall human health. Bacterial species belonging to the genera Lactobacillus and Bifidobacterium are generally considered to be beneficial and are commonly used in probiotic applications, whereas increases in some genera including Clostridum, Eubacterium and Bacteroides are implicated in negative health outcomes. Dietary polyphenols are bioactive compounds that have been found to increase the numbers of beneficial bacteria and antimicrobial actions against pathogenic bacteria, however most studies have been conducted in animal models or in-vitro colonic models. The aim of this systematic review was to provide an overview of recent trials on the effect of dietary grape and red wine polyphenols on the gut microbiota in humans. Following PRISMA guidelines, a systematic review was conducted of electronic databases (PubMed, CINAHL, Cochrane Library, Wed of Science and Scopus) to identify human intervention trials examining the effect of grape or wine polyphenols on gut microbiota. Seven trials met the inclusion criteria. One study looked at changes in gut microbiota following the ingestion of de-alcoholised red wine or red wine, and six studies referred to gut microbiota as intermediates in formation of phenolic metabolites. All studies confirmed that ingested polyphenols from grape and red wine, were modulated by gut microbiota, increasing numbers of polyphenolic metabolites which were found in blood, urine, ileal fluid and faeces. Intake of polyphenols derived from grape and red wine can modulate gut microbiota and contribute to beneficial microbial ecology that can enhance human health benefits. Additionally, grape and red wine polyphenols were modulated by the gut microbiota and there is a potential for a two-way relationship between the gut microbiota and polyphenolic compounds. Nevertheless, additional research is required to fully understand the complex relationship between gut microbiota and dietary polyphenols before any health claims can be made in relation to human health.