Objective To investigate the biomechanical effects of lateral wedge insole (LWI) on internal tissues of the foot and ankle (including foot bones, joints, and ligaments). Methods A three-dimensional finite element model of the foot-insole-ground was developed and validated, and the plantar pressure distributions, contact pressures on joints, and peak stresses on metatarsals and major ligaments in barefoot model and insole intervention models at three key gait instants were explored. Results The 5° LWI model reduced the peak plantar pressure by 65. 8% compared to the barefoot model. Insole interventions decreased the peak contact pressure at the cuneonavicular joint, but increased the peak contact pressure at the subtalar joint and peak stress at the 4th and 5th metatarsals. Conclusions This study quantitatively assesses the biomechanical effects of LWI on various parts of the foot and ankle, and suggests a design that can appropriately reduce the inclination angle of LWI at the 4th and 5th metatarsals.