Oriented strand board (OSB) is an important engineered wood product. The physical and mechanical properties of OSB can be adjusted by optimizing its structural characteristics to fulfill the different application fields. Eight types of boards were produced in the lab in terms of different structural characteristics, including the thickness of surface/core layer, strand’s size and strand’s thickness. Large strands are used in the top/bottom layer of all types of boards. Their physical and mechanical properties were investigated. The results show that the density of the core layer increases with decreasing the size of strands. The orientation angle difference between large (length 150 ± 5 mm×width 35 ± 5) mm) and medium (length 75 ± 5 mm × width 20 ± 2 mm) strands is slight. The modulus of elasticity (MOE) and modulus of rupture (MOR) of all types of boards along major axis are higher than 6500 MPa and 45 MPa respectively. Small strands (length 2 ± 1 mm × width 1 ± 0.5 mm) in the core layer significantly decrease the MOR along the major axis. The MOE and MOR along the minor axis decrease because of small strands in the core layer and thin core layer. Small strands in the core layer are conducive to enhancing the internal bond strength (IB), while thin strands in top/bottom layer significantly decrease the IB. Small strands in the core layer significantly decrease the 24 h thickness swelling. A thin core layer indicates to low screw holding capability in the side face of boards. The outputs of this study contribute to optimizing the production and application strategies of OSB.