Background <p>Emergency department (ED) nurses experience high levels of psychological distress. Practical programs that alleviate psychological distress are essential for enhancing the mental well-being of nurses, which in turn can mitigate the potential adverse effects on the quality of emergency care. However, no systematic review has been conducted.</p> Aim <p>This study aims to systematically summarize the evidence-based psychological distress reduction programs for ED nurses.</p> Methods <p>A systematic search of Web of Science, Scopus, PubMed, and China National Knowledge Infrastructure (CNKI) was conducted for randomized controlled trials published until April 10, 2023. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, and the quality of the qualified studies was assessed using the Cochrane RoB 2 tool.</p> Results <p>A total of 29 studies were eligible with 2058 participants. Three primary kinds of interventions have been identified: psychological interventions targeting the reduction of psychological distress symptoms, educational programs designed to enhance the coping skills of ED nurses, and organization-directed interventions aimed at alleviating stressors. Collectively, these interventions have contributed significantly to the reduction of stress, depression, anxiety, burnout, and post-traumatic stress disorder while also improving life satisfaction and overall quality of life.</p> Conclusion <p>Three types of interventions have provided pathways to alleviate the psychological stress of ED nurses at various levels. Future efforts should refine interventions for ED nurses’ psychological distress, evaluate their long-term benefits, and explore organizational strategies to promote healthier workplaces. Policymakers and administrators must support these initiatives, focusing on prevention and empowerment.</p>