Insider threat is one of the greatest concerns for information security that could cause more significant financial losses and damages than any other attack. However, implementing an efficient detection system is a very challenging task. It has long been recognized that solutions to insider threats are mainly user-centric and several psychological and psychosocial models have been proposed. A user's psychophysiological behavior measures can provide an excellent source of information for detecting user's malicious behaviors and mitigating insider threats. In this dissertation, we propose a multi-modal framework based on the user's psychophysiological measures and computer-based behaviors to distinguish between a user's behaviors during regular activities versus malicious activities. We utilize several psychophysiological measures such as electroencephalogram (EEG), electrocardiogram (ECG), and eye movement and pupil behaviors along with the computer-based behaviors such as the mouse movement dynamics, and keystrokes dynamics to build our framework for detecting malicious insiders. We conduct human subject experiments to capture the psychophysiological measures and the computer-based behaviors for a group of participants while performing several computer-based activities in different scenarios. We analyze the behavioral measures, extract useful features, and evaluate their capability in detecting insider threats. We investigate each measure separately, then we use data fusion techniques …