The incidence of inflammatory bowel disease (IBD), characterized by chronic, relapsing intestinal inflammation, has continually increased in recent years. A previous study by our group identified five potential metabolic markers possibly associated with the pathology of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced IBD in rats. The present study aimed to examine the potential therapeutic effects of the essential oil of Pogostemon cablin (also known as patchouli; PO) on TNBS-induced rats and investigate the concomitant metabolic changes by targeting the previously identified potential markers. Pogostemon cablin is widely used to treat gastrointestinal diseases, including IBD, in China. The results of the present study showed that PO (270 mg/kg, rectal instillation) significantly alleviated colonic damage and reduced disease activity indicators and colonic myeloperoxidase in TNBS-induced rats. In addition, a targeted metabolic profiling study identified that four metabolites were elevated in the urine of the animals in the TNBS group, which were significantly inhibited by treatment with PO: Two tryptophan metabolites [4-(2-aminophenyl)-2,4-dioxobutanoic acid and 4,6-cihydroxyquinoline] and two gut microbial metabolites (phenylacetylglycine and p-cresol glucuronide). Taken together, these findings suggested that PO ameliorated the symptoms of TNBS-induced IBD and reversed the metabolic changes potentially associated with TNBS-induced IBD in rats.