Key message <p>Melatonin enhances rice’s stress resilience by altering stress responses through molecular mechanisms, suggesting innovative strategies for sustainable agriculture amid biotic and abiotic stressors.</p> Abstract <p>Melatonin, a well-known mammalian hormone, is a multifunctional regulator of plant growth, development, and adaptation to stressors. Rice (<i>Oryza sativa</i> L.) yields are under pressure from both biotic and abiotic challenges, which demand robust agricultural practices to ensure food security. Melatonin has attracted considerable attention in rice, owing to its ability to enhance tolerance to diverse abiotic and biotic stressors. Despite significant progress, the molecular and cellular mechanisms underlying melatonin-mediated stress response in rice remain poorly understood. This review summarizes current insights into melatonin biosynthesis, signal transduction, and cross-regulatory networks that coordinate its actions in rice. Particular emphasis is placed on the role of melatonin in mitigating abiotic stresses, such as drought, salinity, extreme temperature, and heavy metal toxicity, as well as strengthening biotic stress tolerance through the modulation of immune signaling and pathogen defense pathways. In addition, we discuss the emerging applications of melatonin-based nanotechnologies, which offer tailored dispersion and sustained bioavailability, as promising tools for enhancing stress resilience in rice. By integrating molecular understanding with nanobiotechnology, this review offers a comprehensive update on the dynamic role of melatonin in the regulation of rice stress. Future research should prioritize unraveling cross-regulatory pathways, along with genetic and biotechnological strategies, to fully exploit the defense potential of melatonin to improve rice productivity and agricultural sustainability under adverse conditions.</p>