• Using a multi-user driving simulator to conduct experiments. • Investigating drivers’ interactive behavior at unsignalized intersections in the connected vehicle environment. • The simplified iterative behavior model has high accuracy and good applicability. • The guidance strategies improve traffic safety, efficiency, and driver comfort. The connected vehicle environment is considered to be a disruptive technology that reconstructs the way people travel and road transport, and more importantly, ensures traffic safety. This study aims on investigating drivers’ interactive behavior at an unsignalized intersection in the connected vehicle environment. Specifically, a simplified iterative behavior model was established to predict the potential conflicting vehicles’ behavior. Furthermore, based on principles of safety, efficiency, and comfort, the guidance strategies were proposed to help the subject vehicles cross intersections. A multi-user driving simulator experiment was carried out and 48 participants were divided into 24 pairs to complete the test. The simplified iterative behavior model was constructed based on the dynamic interaction of each participant pair as they approached the intersection from straight-crossing directions. The comparison results showed the behavior model was an effective microscopic simulation tool for vehicles at unsignalized intersections with high accuracy and good applicability. Then, the guidance strategies under different compliance rates (baseline, 50 % compliance, 100% compliance) were evaluated based on three indexes i.e. standard deviation of speed (SDS), duration of crossing the intersection (DCI), and time exposed post-encroachment-time (TEP). The numerical simulation results showed that the guidance strategies could effectively improve the safety and efficiency of drivers crossing the intersection under both 50% and 100% compliance rates. Besides, with the increase of compliance rate, the comfort level also increased evidently. This study can provide theoretical and algorithmic references for microscopic simulation and guidance strategy at unsignalized intersections in the connected vehicle environment.