Background: Chronic kidney disease (CKD) is a complex health condition that profoundly impacts an individual's general health and well-being throughout their entire lifetime. People with CKD require the knowledge, confidence, and skills to actively self-manage their health. This is referred to as patient activation. The efficacy of interventions to increase patient activation in the CKD population is unclear. Aim: This study aimed to examine the effectiveness of patient activation interventions on behavioral health-related outcomes among people with CKD stages 3–5. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) of patients with CKD stages 3–5 was performed. MEDLINE, EMCARE, EMBASE, and PsychINFO databases were searched between 2005 and February 2021. Risk of bias was assessed using the Joanna Bridge Institute critical appraisal tool. Results: Nineteen RCTs that enrolled 4414 participants were included for synthesis. Only one RCT reported patient activation using the validated 13-item patient activation measure (PAM–13). Four studies demonstrated strong evidence that the intervention group developed a higher level of self-management compared to the control group (standardized mean differences [SMD] = 1.12, 95% CI [0.36, 1.87], p =.004). Eight RCTs led to a significant improvement in self-efficacy (SMD = 0.73, 95% CI [0.39, 1.06], p <.0001). There was weak to no evidence on the effect of the strategies shown on the physical component and mental components of health-related quality of life, and medication adherence. Linking Evidence to Action: This meta-analysis highlights the importance of including tailored interventions using a cluster approach including patient education, goal setting with individualized action plan, and problem-solving to engage patients to be more actively involved in the self-management of their CKD.