Purpose <p>Adults with beta-thalassemia major (BTM) and comorbidities may experience poorer quality of life (QoL), while healthy diet are suggested to improve chronic disease management and health outcomes. The purpose of this study was to explore how healthy diet can impact QoL among adults with BTM, and whether healthy diet can buffer the impact of comorbidities on QoL of this population.</p> Methods <p>Cross-sectional data of 317 adults (18 years old or older) with BTM in Vietnam was analysed. Healthy eating scores was measured by Healthy Eating Scores-5 scale. Four domains of QoL (physical health, psychological, social relationships, and environment) were assessed using the 26-item Quality of Life scale (WHOQOL-BREF). Multivariable linear regression was used to assess the association of interest and its moderation between healthy eating scores and comorbidity status (yes/no).</p> Results <p>Individuals with BTM and comorbidity had significantly a lower QoL score in physical health and social relationships domain than those without comorbidity. This association was inversely moderated by healthy eating scores, specifically in physical health, psychological, and environment domain. As individuals had higher scores in healthy eating, the difference in QoL scores in the three domains above between individuals with and without comorbidities reduced.</p> Conclusion <p>Individuals with BTM and comorbidities have a poorer quality of life. However, encouraging a healthy diet could mitigate this risk. Healthcare system should include dietitians and family caregivers in chronic care management for patients with BTM.</p>