With the global rise in the prevalence of diabetes, diabetic patients need innovative footwear designs to reduce the risk of foot ulcers. This study examined the mechanical properties of diabetic shoe midsoles featuring auxetic lattice structures. Through the construction of finite element models and simulation, this research compared the biomechanical parameter differences in the plantar regions of the metatarsal head, midfoot, and hindfoot when wearing two types of auxetic midsoles with internal angles of 60° and 75° and a non-auxetic midsole with an internal angle of 90° under both walking and running conditions. Compared to the non-auxetic midsole, the auxetic midsoles significantly reduced the peak plantar pressure and optimized the pressure distribution across various plantar regions. Notably, the auxetic 60° midsole reduced the peak plantar pressure by 19.68–55.25% and 16.19–54.39% compared to the non-auxetic 90° midsole during walking and running, respectively. This study also verified that the auxetic midsoles exhibited greater adaptability and compliance to the plantar foot shape, contributing to reductions in plantar pressure in comparisons of deformation values and plantar contact areas across the different midsoles. Auxetic midsoles manufactured using 3D printing technology have significant potential to prevent diabetic foot ulcers and maintain human foot health. This research integrates insights and techniques from materials science and ergonomics, offering a new direction for footwear design.