Objective An X-shaped cushioning insole with variable stiffness was designed to explore its effects on plantar pressure and internal stress of diabetic patients with toe amputation. Methods Based on CT images, the feet-calf finite element model of diabetic patients with toe amputation was established, and the insole was divided into different areas according to distribution characteristics of the planter pressure. The three-dimensional (3D) printed cushioning insole with an X-shaped sandwich structure was designed. The modulus of the sandwich structure was changed by changing thickness of the sandwich structure panel. For simulation analysis, the divided area was filled with the X-shaped sandwich structure with different modulus. Results The peak plantar pressure of diabetic patients with toe amputation was in calcaneal region, and the combined insoles with 1. 2 mpanel thickness in toe area, 1. 4 mm panel thickness in metatarsal area, 2. 0 mm panel thickness in middle area and 1. 6 mm panel thickness in heel area had the best decompression effect. Compared with bare feet, the peak pressure in heel area of the insole, the peak pressure in phalangeal head area and the stress in plantar softissues were reduced by 40. 18% , 31. 7% , and 50. 44% , respectively. Conclusions The 3D printed insoles with variable stiffness can effectively reduce surface pressure and internal stress of the sole and reduce probability of the 2nd toe amputation