Abstract An ankle-foot orthosis (AFO) is the brace that provides the assist and support to the patient with dorsiflexor weakness. However, standard AFO does not provide comfortable fit and is quite heavy for the user. The main objective of this study is redesign the standard AFO based on topology optimization to overcome the problems caused by the standardized AFO. With the computer-aided design (CAD), the AFO is designed based on parameters from the actual size of the adult leg. The thickness and the trim lines were also considered during the design the 3D model. The AFO was simulated with different materials and thicknesses to determine the effect on stress and deflection. Three different thicknesses of AFO; 3mm, 4mm, and 5mm and three different materials; polypropylene (PP), high-density polyethylene (HDPE) and polylactide (PLA) were used in the simulation. Shape optimization technique is used to optimize the material usage in the design of the AFO in order to reduce materials cost and weight. The optimized AFO was compared to the original AFO in terms of strength and flexibility. The 3mm and 4mm average displacement increase to approximately from 23% to 24% to all type of materials during foot flat and heel rise. 4mm model maximum stress decrease by 27% during heel strike, 22% during foot flat, and 20% during heel rise. The weight reduction from the initial AFO model to the optimization AFO model for both 3mm and 4mm thickness is 26% weight reduction and for 5mm thickness, is a 19%.