Inflammatory bowel diseases (IBD) affect the gastrointestinal tract, and the imbalance of intestinal immune homeostasis can trigger them. Pequi oil (PO), a monounsaturated (MUFA) and carotenoid-rich food with nutraceutical potential, could help reshape the intestinal immune response, ameliorating IBD outcomes. This study investigates the effects of a 28 days intake of PO on elements of the intestinal immune response of mice with DSS-induced ulcerative colitis (disease activity index, colonic damage, inflammatory cells and markers). PO reduces body weight, colonic crypt and goblet cell losses and ameliorates diarrhea. In the colon, it increases T cells and secretory-IgA and decreases CD8+T cells. In lymphoid organs, it reduces CD8+T cells. Moreover, it also reduces the IL-17 and CRP in plasma. PO oil promotes a less cytotoxic response that may protect mice from immunological injuries caused by an IBD in the intestinal mucosa, improving the disease prognosis. Practical applications: This study demonstrates that the intake of pequi oil contributes to the regulation of immune response and improves clinical and histological signs of DSS-induced ulcerative colitis in mice. Its effects in cytotoxic cell reduction and other inflammatory markers and stimulation of regulatory cells, and preservation of mucus-producing cells, provide news insights about the importance of the regular intake of this food to better prognosis of ulcerative colitis acute episodes. In addition, these findings encourage further studies with foods with a protective potential for the intestinal mucosa.