Intestinal ischemia–reperfusion (IR) is a frequently occurring phenomenon during abdominal and thoracic vascular surgery, small bowel transplantation, hemorrhagic shock, and surgery using cardiopulmonary bypass, carrying high morbidity and mortality. Ambroxol hydrochloride is an active N-desmethyl metabolite of bromhexine hydrochloride. Ambroxol is indicated as ‘secretolytic therapy in bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport’. Aim The present study was designed to evaluate the effect of ambroxol on experimentally induced acute organ oxidative stress in the form of remote organ injury including kidney and heart after intestinal IR. Materials and methods Thirty animals were classified into five groups. First group: normal control group, second group: nontreated intestinal IR group (intestinal IR was induced by mesenteric artery ligation), third group: ambroxol pretreated intestinal IR group (35 mg/kg), fourth group: ambroxol pretreated intestinal IR group (70 mg/kg), fifth group: ambroxol pretreated intestinal IR group (140 mg/kg). Results Ambroxol significantly reduced the malondialdehyde level in the heart and the kidney when compared with intestinal IR with no medication group. It also improved cardiac troponin and, kidney functions (urea and creatinine) and histopathological affection when compared with intestinal IR with no medication group. Conclusively, in this study ambroxol could have a protective effect against intestinal IR through its antioxidative and anti-inflammatory effect.