The alignment design indexes of highway turning section have important influences on the safety performance of guardrail. In this paper, based on the finite element software LS-DYNA widely used in the field of highway side safety, a complex collision test model of truck and concrete guardrail is established, and simulation and vehicle tests are performed to comparatively verify the effectiveness of the model. Detailed animation describing the collision of vehicle to guardrail is obtained by simulation, which directly exhibits the safety performance of the guardrail in flat curve section. Then, the traffic lane radius, the superelevation value and the vehicle speed are used as variables to investigate and quantify the influence of main alignment indexes on the safety performance of concrete guardrail. The results show that, when the traffic lane radius is close to the ultimate minimum radius corresponding to the design velocity, the roll-over-angle of the vehicle increases, and the vehicle easily crashes to the guardrail and rolls over; that a superelevation value of 6% of the traffic lane is the critical point for the safety performance of concrete guardrail; that when the superelevation value is more than 6%, the height of the vehicle climbing along the collision surface of the guardrail may increase, and the vehicle is more likely to roll over, so that the combination of large superelevation (above 6%) and small ultimate minimum radius should be avoided during the highway design; and that, on the curve section, the collision speed has a significant impact on the safety performance of guardrail. For the integral van, the risk of rollovers significantly increases when the vehicle speed reaches 90 km/h. This research lays a theoretical foundation for the alignment safety design of highway curve sections.