The increasing integration of autonomous systems with publicly available networks exposes them to cyber attackers. An adversary can launch a man-in-the-middle attack to gain control of the system and inflict maximum damages with collision and suicidal attacks. To address this issue, this work establishes an integrative game and control framework to incorporate security into the automatic designs, and take into account the cyber-physical nature and the real-time requirements of the system. We establish a cyber-physical signaling game to develop an impact-aware cyber defense mechanism and leverage model-predictive control methods to design cyber-aware control strategies. The integrative framework enables the co-design of cyber-physical systems to minimize the inflicted systems, leading to online updating the cyber defense and physical layer control decisions. We use unmanned aerial vehicles (UAVs) to illustrate the algorithm, and corroborate the analytical results in two case studies.