Background: End-stage kidney disease (ESKD) imposes a significant global health burden, with patients often experiencing poor quality of life (QoL) due to psychological distress and low self-efficacy. Digital health interventions (DHIs) offer potential to address these challenges. However, their effects in this population remain inconsistent, and a comprehensive synthesis of the evidence is lacking. Objective: To assess the impact of DHIs on the psychological health, self-efficacy, and QoL of ESKD patients, and to evaluate engagement, adherence and satisfaction with these interventions. Methods: A comprehensive search was conducted across six electronic databases (PubMed, Web of Science, Cochrane Library, PsycINFO, Embase, and CINAHL) up to January 21, 2025. Randomized controlled trials (RCTs) examining DHIs effects on psychological health, self-efficacy, or QoL in ESKD patients were included. Two reviewers independently screened studies, extracted data, and assessed the risk of bias using the RoB 2 tool. Meta-analysis was performed using Review Manager 5.4, with subgroup analyses by treatment modality, intervention type, and duration. Evidence quality was assessed using the GRADE approach. Results: 23 RCTs involving 2407 ESKD patients from 12 countries were included. DHIs significantly improved depression (SMD: -0.41, 95% CI: [-0.63, -0.19], P=.003) and overall QoL (SMD: 0.55, 95% CI: [0.07, 1.03], P=.03). While DHIs did not significantly improve overall self-efficacy (SMD: 0.56, 95% CI: [-0.06, 1.18], P=.08), a benefit was observed in hemodialysis patients (SMD: 0.59, 95% CI: [0.34, 0.83], P<.001 engagement was favorable with completion rates above adherence of and generally positive patient feedback on dhis. application-based interventions improved self-efficacy ci: p overall qol telemedicine depression video-based due to high heterogeneity risk bias evidence quality rated as low for moderate general anxiety very stress self-efficacy. conclusions: dhis can significantly improve the psychological health eskd patients particularly when tailored needs delivered through interactive platforms such applications telemedicine. suggest good acceptability in clinical practice. however warrants cautious interpretation. future research should involve more high-quality rcts design that address unique elderly peritoneal dialysis kidney transplant recipients. trial: prospero crd42024629357 https:>