Patients with Duchenne muscular dystrophy (DMD) develop severe skeletal and cardiac muscle pathologies, which result in premature death. Therefore, the current therapeutic efforts are mainly targeted to correct dystrophin expression in skeletal muscle and heart. However, it was reported that DMD patients may also exhibit gastrointestinal and nutritional problems. How the pathological alterations in gastrointestinal tissues may contribute to the disease are not fully explored. Here we employed the CRISPR/Cas9 system combined with somatic nuclear transfer technology (SCNT) to establish a porcine model of DMD and explored their pathological alterations. We found that genetic disruption of dystrophin expression led1 to morphological gastrointestinal tract alterations, weakened the gastrointestinal tract digestion and absorption capacity, and eventually led to malnutrition and gastric dysfunction in the DMD pigs. This work provides important insights into the pathogenesis of DMD and highlights the need to consider the gastrointestinal dysfunction as an additional therapeutic target for DMD patients.