Objective To explore the mechanism of ankle sprain varus, a kind of human ankle brace with asymmetric physiological structure which can protect the ankle effectively is designed. Methods The anatomic factors of ankle varus were analyzed firstly, and a kind of ankle brace with asymmetric structure was designed based on asymmetric structure of ankle joint by anatomy. Using Kinect system and Geomagic Studio software, 3D scanning and digital modeling on ankle joint of a male adult were performed, and the ankle model was established by 3D printing technology. With EVA film, silica gel film and wrapped edge copper network as raw materials, two kinds of ankle brace with asymmetric structure were prepared by 3D draping and composite materials processing technology. The shaping properties, tensile properties, fatigue performance, outer fabric breathability and friction of the designed brace were tested. Results The outside of ankle brace with asymmetric structure had good shaping property, low tensile elastic recovery rate. Under the effect of repeated small load, EVA composite materials and silicone composite materials could keep good elastic recovery and effectively bear external varus forces. The results from air permeability and grinding test showed that polyester material was a kind of suitable fabrics for the outer lining material. Conclusions The mechanical properties of ankle brace with asymmetric structure can meet the requirement of ankle varus protection. The fabric of ankle brace can improve moisture permeability and frictional properties.