In order to quantify the influence of uncertainties in the terminal guidance initial parameters for unpowered gliding vehicle, an uncertainty-based design optimization method of terminal guidance initial parameters was developed to improve the accuracy of impact point. The sliding-mode variable structure control was used to predict trajectory of vehicle in real time to meet the requirements of high dynamic strike in the terminal stage of flight vehicle. In consideration of the uncertainties in the terminal guidance initial parameters, the optimization model of uncertainty-based terminal guidance initial parameters and guidance law parameters was built. The circular error probability and the probability of impact points in the effective damage radius were considered into the multiple-objective function. Effective global optimization and Monte Carlos method were used to obtain the optimum of initial parameters and guidance law parameters efficiently. It was shown that the accuracy of impact point is improved significantly, which can further provide decision support for the connection point of terminal guidance in the stage of vehicle conceptual design.