In this paper, we propose a system-level optimization approach for mixed-criticality distributed real-time systems with safety and energy considerations. We firstly depict a mixed-criticality distributed task model for real-time applications, in which the safety of the system is influenced by dynamic voltage and frequency scaling (DVFS). Due to the huge complexity of solving the problem optimally, a heuristic algorithm is proposed to approach the system-level optimization through a quasi-static scheduling strategy. The experiments demonstrate the efficiency of the proposed approach, which can obtain energy consumption while guaranteeing the system safety requirements.