Background With the advent of electronic health record (EHR) systems, there is increasing attention on the EHR system with regard to its use in facilitating patients to play active roles in their care via secure patient portals. However, there is no systematic review to comprehensively address patient portal interventions and patient outcomes. Objective This study aimed to synthesize evidence with regard to the characteristics and psychobehavioral and clinical outcomes of patient portal interventions. Methods In November 2018, we conducted searches in 3 electronic databases, including PubMed, EMBASE, and Cumulative Index to Nursing and Allied Health Literature, and a total of 24 articles met the eligibility criteria. Results All but 3 studies were conducted in the United States. The types of study designs varied, and samples predominantly involved non-Hispanic white and highly educated patients with sizes ranging from 50 to 22,703. Most of the portal interventions used tailored alerts or educational resources tailored to the patient’s condition. Patient portal interventions lead to improvements in a wide range of psychobehavioral outcomes, such as health knowledge, self-efficacy, decision making, medication adherence, and preventive service use. Effects of patient portal interventions on clinical outcomes including blood pressure, glucose, cholesterol, and weight loss were mixed. Conclusions Patient portal interventions were overall effective in improving a few psychological outcomes, medication adherence, and preventive service use. There was insufficient evidence to support the use of patient portals to improve clinical outcomes. Understanding the role of patient portals as an effective intervention strategy is an essential step to encourage patients to be actively engaged in their health care.