The automotive industry is repeatedly tasked with improving vehicles structural strength, optimizing active and passive safety features, reducing occupant injury potential, and hitting lean manufacturing goals. The challenge is to find solutions to reduce production and research costs, and to maximize the vehicle's capability in protecting its occupants in the event of an accident. The influence of impact loading on the dynamic responses of vehicle structures and occupants require special consideration in the field of vehicle crashworthiness. The main goal of this study is to address the fundamental aspect on the impact injury biomechanics of vehicle occupants and safety performance of vehicle structures, and the development of various new technologies aimed at enhancing the passive safety of road vehicles in side-impact accidents. Four case studies related to the dissipation of crash energy, impact injury biomechanics, injury prediction model and pre-crash sensing algorithm form the basis of this thesis. The application examples include the investigation of pre-deploying airbags as a potential solution in reducing occupants' injuries at higher speed side-impact crashes; examination of the vehicle structural responses with the inclusion of high-energy absorbing cellular materials within the door panels in side-impact accidents; development of injury prediction model to out-of-position occupants from frontal- and side- airbags using Design-of-Experiment methodologies; and the estimation of the relative driver fatality risks of two colliding vehicles using some quantitative measurements. A detailed methodology is developed for each application, and the results present several new technologies that can be implemented to enhance the safety performance of road vehicles. These goals are achieved through the use of finite element approaches, multi-body dynamic analyses and Design-of-Experiment statistical methods.