Grape peel, as the by-product of grape wine, is rich in phenolic and proanthocyanidins. Obesity has become a serious global public health problem and supplementation of grape peel phenolics (GPP) may be an effective intervention method. From a dietary nutrition perspective, this study aims to investigate the effects of GPP on improving intestinal barrier function in high-fat diet-treated mice, and further explore the potential mechanism. The results showed that GPP supplementation obviously reduced body weight of mice, increased the abundance of beneficial bacteria (Akkermansia, g_Lachnospiraceae_NK4A136_group, Bacteroidetes and g_norank_f_Muribaculaceae), reduced the relative abundance of harmful bacteria (g_Coriobacteriaceae_UCG-002, g_Dubosiella and Romboutsia). Meanwhile, GPP could alleviate colonic barrier inflammation, facilitate the production of short-chain fatty acids and secondary bile acids, increase the mRNA and protein expression levels of intestinal tight junction proteins, and protect intestinal barrier integrity, especially in the LGPP group (100 mg/kg∙day GPP). Kyoto Encyclopedia of Genes and Genomes analysis on fecal metabolism indicated that GPP could effectively alleviate intestinal imbalance caused by obesity through targeting multiple shared pathways. Bile secretion and arachidonic acid are the key differential metabolic pathways, and 14 key differential metabolites were identified. In conclusion, GPP supplementation has the potential to alleviate obesity by regulating gut microbiota, improving gut barrier integrity, and modulating the related metabolites.