The Bama diet (BD), Mediterranean diet (MD), and Japanese diet (JD) are three typical dietary patterns from distinct geographical regions. The aim of this study was to compare the efficacy of three diets in preventing colitis through gut microbe-metabolite-mediated regulatory mechanisms. This was achieved by integrating gut microbiome and metabolomics analyses. Results showed that BD could significantly increase the level of interleukin 10 (IL-10), which has the potential to modulate the intestinal immune response. This was achieved by modulating the α-linoleic acid metabolism and promoting Akkermansia proliferation. MD elevated IL-10 level and increased the expression of tight junction proteins such as occludin, claudin-1, and zonula occludens-1. This effect might be attributed to the increased abundance of bifidobacteria, which impacted the primary bile acid biosynthesis pathway. JD decreased tumor necrosis factor α level and increased IL-10 level. This could be due to JD promoting the enrichment of Faecalibacterium, which affected the metabolism of arachidonic acid. Furthermore, the anti-inflammatory effects of the different metabolites, namely α-linoleic acid, cholic acid, and arachidonic acid, were confirmed using the RAW264.7 cellular inflammation model.