The protein dystrophin is a component of the dystrophin-associated protein complex which links the contractile machinery to the plasma membrane to the extracellular matrix. The absence of dystrophin leads to a pathological condition known as the Duchenne muscular dystrophy (DMD), a disease characterized by a progressive skeletal muscle degeneration, disability, and early death. The mdx mice is the most common DMD animal model. Alterations in gastrointestinal tissues from DMD patients and mdx mice are scarcely described, and little understood. Using isolated tissue samples, explanted from mdx and control mice, we thus investigated the possible relationships between possible morphological and contractile properties impairments with alterations in the calcium handling due to the absence of the protein dystrophin in the mdx mice ileum. Absence of dystrophin caused 27% reduction in the longitudinal muscular layer thickness, accompanied by a partial damage to the mucosa layer (Chiu score of 2-4 by dystrophic animal in comparison with 0-2 score in control), and a partial damage to the mitochondria from the longitudinal muscular layer. Functionally, it was shown a higher resistance to basal tissue stretching (as the contractile response under 1 g-basal tension in mdx is maintained the same as under the optimal 0.5 g-basal tension in mdx mice. In control mice, the responses under 1 g-basal tension are already diminished) and impairment in the Emax (maximum effect) of both eletro- (mdx: 2.36 ± 0.09 g and control: 2.77 ± 0.13 g) and pharmacomechanical (mdx: 2.47 ± 0.09 g and control 2.95 ± 0.12 g) signaling associated with altered calcium influx (half-life time of 1.2 min in mdx mice compared to 0.4 in control stimulation with KCl successive stimuli), without any alteration in the sarcoplasmic reticulum calcium storage (maintenance of the caffeine-induced contraction, 1.12 ± 0.07 g in control and 0.98 ± 0.05 g in mdx mice), in the ileum isolated from the dystrophic animal as compared to control animals. It is thus concluded that intestine is sensitive to the dystrophic condition, as the protein dystrophin plays an important role in the preservation of both the micro and ultra structure of mice intestine, while exerting minor roles concerning both the intestinal contractile responsiveness and the SR calcium storage capacity and release in dystrophic mice.