Background <p>Chronic diseases require ongoing self-management, but patients often struggle with knowledge, behavioral adherence, and emotional well-being. Virtual nurse interventions, which refers to digital systems simulating nurse–patient interactions, offer a potential strategy to support self-management. This review aimed to evaluate their effectiveness in improving health knowledge, behavioral outcomes, psychological well-being, and patient satisfaction.</p> Methods <p>A systematic search of the Cochrane Library, PubMed, CINAHL, MEDLINE, and EMBASE was conducted for randomized controlled trials published between 2014 and April 2025. Studies involving adults with chronic diseases and virtual nurse interventions reporting outcomes on knowledge, behavior, psychological well-being, or patient satisfaction were included. Methodological quality was appraised using the Joanna Briggs Institute checklist. Data were synthesized narratively using the Synthesis Without Meta-analysis (SWiM) framework due to substantial heterogeneity in intervention modalities and outcome measures.</p> Results <p>Six trials with 533 participants were included. Virtual nurse interventions consistently improved disease-specific knowledge and psychological well-being, and were associated with high patient satisfaction. Evidence for behavioral adherence and clinical outcomes was limited and often not statistically significant.</p> Conclusions <p>Virtual nurse interventions show potential to enhance disease-related knowledge and psychological support among adults with chronic diseases. However, given the small evidence base, their long-term effects on sustained behavioral change and clinical outcomes remain inconclusive. Future research should prioritize rigorous, long-term trials and consider cultural adaptations and digital health literacy to optimize real-world implementation.</p> Clinical trial number <p>Not applicable. Shiouh-Chu Shieh.</p> Trial registration <p>PROSPERO CRD420251038439.</p>