In this paper, we study a mathematical model for evaluating the resistant force of endoscopic devices self-propelling in the small intestine with a consideration of its anatomy. Circular fold is the main source of intestinal resistance that needs to be overcome during the endoscopic procedure. Our model is able to calculate the resistances of such folds in different dimensions. Finite element analysis and experimental testing are presented to validate the proposed model by using a pulling-type endoscopic capsule. Our investigation shows that the resistance reaches its maximum immediately after the capsule is pulled against the fold, and drops off gradually during the crossing motion. The proposed method is further demonstrated by using a magnetic pulling-type capsule prototype in an intestine simulator. The findings of this study provide a better insight into the biomechanics of the small intestine and advance the understanding of capsule–intestine interaction for robotic and endoscopic engineers.