To simulate the biomechanical changes of knee joint before and after wearing the orthosis in patients with knee osteoarthritis (KOA) by constructing a finite element model of the knee joint and a customized additively manufactured knee orthosis, so as to verify the decompression effect of the orthosis, and aimed at orthopaedics, a quantitative research on the therapeutic effect of knee orthosis was conducted to evaluate the clinical efficacy of knee orthosis.This experiment was approved by the Ethics Committee of the Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. A woman with knee osteoarthritis was recruited, and the knee joint was subjected to optical body surface and CT scans. A custom-made additively manufactured knee orthosis was designed according to the principle of unilateral decompression. After boundary setting and other steps, software such as ANSYS was used to build a finite element model of the knee joint and a customized additively manufactured knee joint orthosis. By applying a compressive load of 1100 N to the knee joint along the direction of the lower limb load-bearing axis, a simulation and stress analysis was performed to study the deloading effect of a custom additively manufactured knee orthosis on the knee compartment. A finite element analysis of KOA characteristics was conducted for verification, considering the influence of cartilage, ligament, and lower limb skin on the bearing capacity of the knee joint. Compared with the case without wearing any orthosis, after wearing the customized knee orthosis, the varus angle of the knee joint was reduced, the medial pressure of the knee joint was shifted to the lateral side, and the pressure of the medial compartment of the knee joint was significantly reduced. The custom additively manufactured knee orthosis can reduce the pressure generated by the medial compartment of the knee joint during walking in patients with early and mid-stage medial compartment knee osteoarthritis, and the load reduction effect is significant.