PURPOSE: This systematic review aims to summarize the mental health outcomes of self-employment and identify potential moderators between self-employment and mental health issues, ultimately guiding future research and informing targeted suggestions for future practice. METHOD: The initial search identified 3412 publications, including 43 that met the inclusion criteria. We identified 20 potential moderators in total. RESULTS: According to the summary results based on the diathesis-stress model, gender, financial precarity, and social security were identified as the most frequent potential moderators in each domain. DISCUSSION: The systematic review highlights the complex relationship between self-employment and mental health, revealing that self-employment often correlates with negative mental health outcomes such as stress and depression. Future practice should prioritize financial stability strategies, gender-specific support initiatives, work-life balance improvements, and expanded social security protections for self-employed workers.