Objective <p>The hospitalization of a premature infant in a neonatal intensive care unit (NICU) is a stressful experience for mothers, often reducing their quality of life (QoL). This study evaluated the effect of a peer-led educational and supportive program on the QoL of mothers with premature infants. A quasi-experimental study was conducted in the NICUs of Hazrat Vali-e-Asr Hospital, Tehran, Iran. Seventy mothers were enrolled and non-randomly assigned to an intervention group (<i>n</i> = 35) or a control group (<i>n</i> = 35) based on the ward where their infant was hospitalized. The intervention group attended three peer-led sessions over ten days. The control group received standard NICU education from nurses. QoL was measured using the Short Form Health Survey (SF-36) at baseline and one month after the intervention. Data were analyzed using independent t-tests and ANCOVA.</p> Results <p>At baseline, there was no significant difference in QoL scores between groups (<i>P</i> = 0.89). Post-intervention, the intervention group showed significantly higher total QoL scores than the control group (<i>P</i> &lt; 0.001). Significant improvements were noted in mental health, vitality, social functioning, and role limitations due to emotional problems (all <i>P</i> &lt; 0.001). These findings suggest peer-led programs can improve maternal QoL in NICUs and support their integration into neonatal care.</p> Trial registration <p>This study was retrospectively registered in the Iranian Registry of Clinical Trials on July 20, 2025 (IRCT20230816059164N4; <a href="https://irct.behdasht.gov.ir/trial/84566">https://irct.behdasht.gov.ir/trial/84566</a>).</p>