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Rational drug use is a pivotal concept linked with morbidity and mortality. Immigration plays a significant role as a determinant affecting individuals' health-related attitudes, behaviors, and the pursuit of health services. Within this context, the study was initiated to assess the factors influencing health literacy and rational drug use among Syrian immigrants in Istanbul. A cross-sectional study was undertaken on 542 Syrian adults utilizing a three-part questionnaire encompassing sociodemographics, rational drug use, and the e-health literacy scale (eHEALS). With an average age of 39.19 ± 13.10 years, a majority of participants believed medications should solely be doctor-prescribed (97%) and opposed keeping antibiotics at home (93.7%). Yet, 62.5% thought excessive herbal medicine use was harmless. The mean eHEALS score stood at 20.57 ± 7.26, and factors like age, marital status, income, and duration of stay in Turkey influenced e-health literacy. Associations were seen between low e-health literacy and being female, being older, having a lower education level, and regular medication use. Syrian immigrants displayed proper knowledge concerning antibiotics yet exhibited gaps in their understanding of general drug usage, treatment adherence, and herbal medicines. Approximately 80.3% had limited health literacy, pointing to the need for targeted interventions for enhanced health and societal assimilation. [ABSTRACT FROM AUTHOR]