In safety-critical computing systems, the I/O virtualization must simultaneously satisfy different requirements, including time-predictability, performance, and energy-efficiency. However, these requirements are challenging to achieve due to complex I/O access path and resource management at the system level, lack of support from preemptive scheduling at I/O hardware level, and missing an effective energy management method. In this paper, we propose a new framework, I/O-GUARD, which reconstructs the system architecture of I/O virtualization, bringing a dedicated hardware hypervisor to handle resource management throughout the system. The hypervisor improves system real-time performance by enabling preemptive scheduling in I/O virtualization with both analytical and experimental real-time guarantees. Furthermore, we also present a dedicated energy management unit to adjust I/O-GUARD's dynamic energy using frequency scaling. Associated with that, a frequency identification algorithm is proposed to find the appropriate executing frequency at run-time. As shown in experiments, I/O-GUARD simultaneously improves the predictability, performance and energy-efficiency compared to the state-of-the-art I/O virtualization.