Solanum lycocarpum St. Hil. is considered a natural anti-inflammatory. In traditional medicine, it is used to reduce cholesterol levels in the treatment of obesity. Foods capable of conferring a protective and nutritious effect have been used to prevent or attenuate the clinical symptoms of inflammatory bowel diseases. Ulcerative colitis is a multifactorial inflammatory bowel disease. This study investigated the impact of the consumption of the fibrous fraction (FF) and resistant starch (RS) of fruta-do-lobo in an experimental model of colitis induced with the use 2,4,6-trinitrobenzene sulphonic acid (TNBS) in rats. The different colitis groups all experienced decreased weight gain, which could be linked to the inflammatory process (p = 0.603). Additionally, the experimental model led to increased oxidative stress, higher levels of pro-inflammatory cytokines, and the elevated gene expression of these cytokines. Despite this, consuming the fibrous fraction of fruta-do-lobo (RS and FF) did not appear to protect the animals against the inflammatory process. Regarding the expression of TNF-α, only the group treated with the drug mesalamine had a reduced serum level of this inflammatory marker (p = 0.03). Our results showed that the diet containing RS and FF did not protect the intestinal mucosa against TNBS inflammation. New studies on the variation in the time of consumption or the supplemented dose of fruta-do-lobo fibers could help to elucidate their effects in protecting the mucosa.