In this paper, we propose CPS-Guard, a novel framework for verification and validation (V&V) of AI-based cyber-physical systems (CPSs). CPS-Guard automates the iterative assurance process through multi-role coordination, assigning specialized agents (e.g., safety monitoring, security assessment, fault injection, recovery planning) within a simulation environment to continuously evaluate and improve AI behaviors according to various reliability requirements. We verify the effectiveness of CPS-Guard through an intersection crossing scenario of an autonomous vehicle, and show that it provides a structured and scalable solution for rigorous V&V of safety- and security-critical systems by detecting vulnerabilities, managing performance impacts, and supporting adaptive recovery strategies.