We hypothesized that dragon fruit extract (DFE) might be a protective agent in oxidative stress damage that develops against ischemia and reperfusion injury in the rat intestine. The rats used in the study were randomly divided into 8 groups, with 6 animals in each group. The HEALTHY group was not induced by ischemia and not given DFE (Group 1). The DFE1000 group was not induced by ischemia; however, DFE was given 1000 mg/kg (Group 2). Ischemia was induced for 1 h in groups 3, 4, 5, 6, 7 and 8. The clamps were then removed to allow reperfusion for 45 min (Groups 6, 7 and 8). DFE was given to rats at doses of 500mg/kg and 1000 mg/kg 30 min before Ischemia (I) and Ischemia/Reperfusion (I/R) administration. At the end of the experiment, histopathological, biochemical and molecular analyses were performed on the intestinal tissues. While glutathione peroxidase, superoxide dismutase, glutathione levels increased significantly in the I+DFE500, I+DFE1000, I/R+DFE500 and I/R+DFE1000 groups compared to the I and I/R groups, there was a significant decrease in tumor necrosis factor-α, Caspase 3 and malondialdehyde (P<0.05). In addition, the loss of tissue integrity, and the increase of inflammatory cells were decreased in the treatment groups. As a result, it was determined that DFE has a strong protective role against oxidative damage in the treatment of intestinal ischemia-reperfusion injury.