A fuzzy variable coefficient variable structure guidance law is designed for intercepting high-speed maneuvering targets with terminal line-of-sight angle constraints. Firstly, an adaptive variable structure guidance law is proposed to adaptively adjust the velocity approaching the sliding mode surface according to the distance of the missile target. Then, the chattering is eliminated by replacing the switch term in guidance law with the saturation function. Simulation results show that the proposed guidance law can meet the requirements of line-of-sight angle constraint and miss distance for intercepting high-speed non-maneuvering and maneuvering targets, but it requires a large overload. To this end, a fuzzy control method is introduced and a fuzzy controller is designed to optimize the guidance coefficient in the variable structure guidance law. Finally, a fuzzy variable structure guidance law with a variable coefficient is obtained to satisfy the line-of-sight angle constraint and restrain the required system overload.