Field Programmable Gate Arrays (FPGAs) enter a rapid growth era due to their attractive flexibility and CMOS-compatible fabrication process. However, the increasing popularity and usage of FPGAs bring in some security concerns, such as intellectual property privacy, malicious stealthy design modification, and leak of confidential information. To address the security threats on FPGA systems, majority of existing efforts focus on counteracting the reverse engineering attacks on the downloaded FPGA configuration file or the retrieval of authentication code or crypto key stored on the FPGA memory. In this thesis, we extensively investigate new potential attacks originated from the untrusted computer-aided design (CAD) suite for FPGAs. We further propose a series of countermeasures to thwart those attacks. For the scenario of using FPGAs to replace obsolete aging components in legacy systems, we propose a Runtime Pin Grounding (RPG) scheme to ground the unused pins and check the pin status at every clock cycle, and exploit the principle of moving target defense (MTD) to develop a hardware MTD (HMTD) method against hardware Trojan attacks. Our method reduces the hardware Trojan bypass rate by up to 61% over existing solutions at the cost of 0.1% more FPGA utilization. For general FPGA applications, we extend HMTD to a FPGA-oriented MTD (FOMTD) method, which aims for thwarting FPGA tools induced design tampering. Our FOMTD is composed of three defense lines on user constraints file, random design replica selection, and runtime submodule assembling. Theoretical analyses and FPGA emulation results show that proposed FOMTD is capable to tackle three levels' attacks from malicious FPGA design software suite.