Minimally invasive surgery is a developing direction of modern medicine. With the successful development of controllable capsule endoscopies, capsule robots are very popular in the field of gastrointestinal medicine. At present, the study of intestinal robots is aimed at the pipeline environment of a single-phase liquid flow. But there exist food residues (i.e. solid particles) or liquid foods in the actual intestine, so intestinal fluid should be liquid–solid or liquid–liquid two-phase mixed fluid. For inner spiral capsule robots with different internal diameters and outer spiral capsule robots, using computational fluid dynamics (CFD) method, the operational performance indicators (i.e. axial thrust force, circumferential resisting moment and maximum pressure to pipeline wall) of spiral capsule robots are numerically calculated in the liquid–solid or liquid–liquid two-phase mixed fluid. By the orthogonal experimental optimization method, the optimum design of spiral capsule robots is obtained in the liquid–solid mixed fluid. The experimental verification has been also carried out. The results show that in the liquid–solid two-phase fluid, the axial thrust force and circumferential resisting moment of the spiral capsule robots decrease with the increase of the size or concentration of solid particles. In the same liquid–solid or liquid–liquid mixed fluid, the operational performance indicators of outer spiral robots are much higher than those of inner spiral robots, and the operational performance indicators of inner spiral robots with bigger internal diameters are higher than those with smaller internal diameters. Adding solid particles of high concentration in the pipeline containing liquid will reduce the drive performance of spiral capsule robots, but adding another liquid of high viscosity will improve the drive performance of spiral capsule robots.