As more long-span bridges continue to be completed and opened to traffic, the safety of cars driving across the bridge has attracted more and more attention, especially when the car is suddenly affected by the crosswind, the car is likely to have direction deviation or even a rollover accident. In this paper, the large eddy simulation method is used to study the flow field characteristics and safety of the car on the bridge under the turbulent crosswind. The numerical simulation model is established by referring to the Donghai Bridge, and the correctness of the car model is validated by combining with the data of wind tunnel test. The influence of factors such as the porosity and height of the bridge guardrail and the Reynolds number of airflow on the flow field characteristics is analyzed. The study shows that, in order to ensure the safety of cars on the bridge, the bridge guardrail porosity should be small, 35.8% is more suitable, the guardrail height should be more suitable within the range of 1.5–1.625 meters, and the Reynolds number should not be 3.51e + 5. The research results of this paper will provide reference for the optimal design of bridge guardrail.