Mat foundations are widely employed in structural engineering applications where the supporting soil exhibits relatively low bearing capacity. In recent years, the adoption of prestressing techniques in foundation and superstructure systems has attracted increasing attention due to their potential to enhance structural performance and improve material efficiency. However, limited research has been conducted to systematically compare the behavior of reinforced and prestressed concrete mat foundations under varying soil conditions. This study investigates the structural performance of mat foundations while accounting for the effects of soil-structure interaction. Three representative values of the soil subgrade reaction modulus were considered to simulate weak, medium, and stiff soil conditions. A comprehensive finite element analysis was conducted to evaluate and compare the responses of prestressed and non-prestressed mat foundations under identical loading scenarios. The numerical results demonstrate that the subgrade reaction modulus significantly influences the distribution of soil bearing pressures and bending moments within both reinforced and prestressed mat foundations. The findings further indicate that the application of prestressing techniques markedly enhances the structural performance, serviceability, and overall economic efficiency of mat foundation systems.