Inflammatory bowel disease is a collection of intestinal disorders that cause inflammation in the digestive tract. Prolonged inflammation in the gastrointestinal tract is a major risk factor for colorectal cancer. The objective of this study was to fucus on gene expression levels of (KRT-14; associated with epithelial cell integrity) and enhancer of zeste homolog-1 (EZH-2; involved in cellular proliferation) in a IBD rat model in order to rule out impact of nutraceuticals (pumpkin seed oil; PSO) as a complementary approach to conventional treatments of IBD. In the current study, IBD was induced using dextran sodium sulfate (DSS). Following acclimatization, rats were separated into three groups: the negative control, the positive control, and the treatment group. The DSS (1 ml/kg bw) was given to the positive control and treatment groups. Negative control was given only a normal diet. Pumpkin seed oil (PSO) was given orally as a treatment (0.5 ml/kg bw). Blood and colon tissue were obtained on the 5th, 10th, 14th, and 18th days. Physical parameters, hematology, biochemical assays, gene expression, and histopathology were carried out. After statistical analyses, macroscopic parameters showed significant differences. Biochemical analyses revealed a significant (P ≤ 0.05) decrease in serum potassium concentrations, total cholesterol, triglycerides, total proteins, total oxidants status, and C-reactive proteins in PSO treated group as compared with positive control. Gene expression levels of KRT-14 and EZH2 were significantly (P ≤ 0.05) upregulated in PSO treated group as compared to positive control group. Histopathology revealed that pumpkin seed oil preserved the structural integrity of colon.