Increasing death figures for pedestrian accidents on the roadside has made it one of the most important problems to overcome worldwide. Increasing demand for pedestrian protection is taking a significant role for the automotive manufacturers for vehicle designs that minimize pedestrian injuries and fatalities. During a collision event, it is essential to understand the pedestrian-vehicle kinematics and injury mechanisms by examining the biomechanical responses and the vehicle front-end profile. In this study, pedestrian impact analyses with full-size human models (AM 50th-THUMS) are first carried in the Finite Element (FE) LS-DYNA workbench to explore the kinematics and injury parameters in a pedestrian-car collision. Due to their computational cost and their lack of models availability issues, modeling and simulations are then investigated in the multi-body MADYMO workbench instead. Multi-body ellipsoidal car models are developed and utilized along with different pedestrian models of different sizes. The comparison of results are performed with a Design of Experiment (DOE) approach to investigate the importance of different design parameters. The full-size pedestrian responses are quite sensitive to many impact conditions such as the exact location and the speed of impact. Pedestrian subsystem impactor models are then developed and utilized for better assessment of pedestrian kinematics. The upper legform, lower legform, and adult headform models are individually utilized to examine the potential injuries using FE simulations. The development of a simplified FE model of the Flex-Pli for its biofidelic structure is carried out to examine the pedestrian lower extremities during the impact. Another aspect of this study represents the material selection for a vehicle hood and frontal-end, for better protection of pedestrians. The models, methods, and results from this study can be utilized in the design of vehicle front-end such as hood, bumper, etc. along with material changes and therefore investigation of potential injuries and fatalities to pedestrians as well as development of future pedestrian impact protection regulations.