Background <p>Major Depressive Disorder (MDD) is one of the most prevalent mood disorders, and internalized stigma remains a significant challenge faced by individuals. Novel therapeutic approaches, such as Eye Movement Desensitization and Reprocessing (EMDR), may help address this issue. This study aimed to investigate the effect of EMDR on internalized stigma in patients with MDD.</p> Methods <p>This study was a Randomized Controlled Trial (RCT) that included 66 patients with MDD at Shahid Rajaei Hospital in Yasuj, Iran, in 2025. Patients were selected using convenience sampling and randomly allocated to either the intervention group (<i>n</i> = 33; receiving seven individual EMDR sessions, each lasting 45–90&#xa0;min) or the control group (<i>n</i> = 33; receiving standard treatment). Internalized stigma was assessed using the Internalized Stigma of Mental Illness (ISMI) scale at baseline, post-intervention, and three-month follow-up. Data were analyzed using descriptive statistics, paired and independent t-tests, repeated-measures analysis of variance, and analysis of covariance (ANCOVA) in SPSS version 27.</p> Results <p>The adjusted mean total internalized stigma score in the intervention group was significantly lower than in the control group at post-test (61.37 vs. 93.78) and three-month follow-up (54.02 vs. 97.16) (<i>P</i> &lt; 0.01). A significant improvement was also observed across all subscales (Alienation, Stereotype Endorsement, Perceived Discrimination, Social Withdrawal, and Stigma Resistance) in favor of the intervention group at both time points (<i>P</i> &lt; 0.001).</p> Conclusions <p>EMDR is an effective and non-invasive intervention that helps reduce internalized stigma in patients with MDD.</p> Trial registration <p>Iranian Registry of Clinical Trials (IRCT): IRCT20250111064354N1. Registered 9 March 2025, retrospectively registered.</p>