Objective: To investigate the effect of wheat peptides on intestinal damage from non-steroidal anti-inflammatory drugs(NSAIDs). Methods: The 4-week-old male KM mice were randomly divided into 6 groups according to body weight， namely blank group (saline gavage)， diclofenac sodium group (diclofenac sodium gavage)， glutamine group (diclofenac sodium + glutamine)， wheat peptide low， medium and high dose groups (diclofenac sodium + different doses of wheat peptide)， 10 mice in each group， and treated continuously for 21 days. Mice were fasted for 12 h after the final gavage and weighed. Mice were subjected to blood sampling for oxidative stress levels and adrenaline E2 (PGE2) assays. Mouse intestine tissue was collected for histopathological testing and western blot was used to detect the expression of intestinal tissue tight junction proteins. Results: Compared with the diclofenac sodium group， mice in the wheat peptides and glutamine groups had higher body weights， lower levels of oxidative stress and restored PGE2 expression to normal levels. The mucosal barrier damage in mouse intestinal tissues was improved and the expression of tight junction protein was increased. Conclusion: Wheat peptides have protective effects against diclofenac sodium-induced intestinal disorders. It is promising to provide an effective method to protect against NSAIDs intestinal barrier function impairment.