Background Learning disabilities (LD) and attention-deficit hyperactivity disorder (ADHD) are often accompanied by significant socio-emotional impairments and mental health challenges. However, there is a lack of controlled, quantitative research on potential interventions to address this issue. The current study evaluated the impact of a near-peer mentoring program for youth with LD/ADHD designed to promote socio-emotional well-being. Methods Youth with LD/ADHD who participated in the mentoring program (Mentored; n =99) were compared to non-mentored youth with LD/ADHD (Control-NM; n =51) and typically-developing youth without LD/ADHD (Control-TD; n =81) pre-mentoring in the fall, and post-mentoring in the spring. Participants were assessed on self-report measures of anxiety, depression, interpersonal relations, and self-esteem. Results Youth with LD/ADHD showed significantly higher scores of depression and significantly lower scores of interpersonal relations compared to the Control-TD group at fall baseline. The depression and self-esteem scores of the Mentored group significantly decreased and increased respectively after mentoring. These changes were associated with mentee-perceived mentorship quality. The Control-NM group showed significant decreases in both self-esteem and interpersonal relations, as well as increases in depression over time, while the Control-TD group remained stable across all measures. Conclusions Results suggest that mentoring shows promise as a potential intervention for youth with LD/ADHD and co-occurring socio-emotional and mental health difficulties. The study is the first, to our knowledge, to quantify the effect of a near-peer mentoring program on youth with LD/ADHD in a design with two control groups. Implications for research and practice involving LD, ADHD, and mental health disorders are discussed.