Cloud and data center applications increasingly leverage FPGAs because of their performance/watt benefits and flexibility advantages over traditional processing cores such as CPUs and GPUs. As the rising demand for hardware acceleration gradually leads to FPGA multi-tenancy in the cloud, there are rising concerns about the security challenges posed by FPGA virtualization. Exposing space-shared FPGAs to multiple cloud tenants may compromise the confidentiality, integrity, and availability of FPGA-accelerated applications. In this work, we present a hardware/software architecture for domain isolation in FPGA-accelerated clouds and data centers with a focus on software-based attacks aiming at unauthorized access and information leakage. Our proposed architecture implements Mandatory Access Control security policies from software down to the hardware accelerators on FPGA. Our experiments demonstrate that the proposed architecture protects against such attacks with minimal area and communication overhead.