Self-medication is a widely practiced behavior, especially among university students, and is influenced by a variety of socio-economic and cultural factors. This cross-sectional study investigates self-medication practices among university students in Bangladesh and Malaysia, focusing on the prevalence, types of drugs used, reasons for self-medication, and the awareness of its associated risks. A total of 731 students (514 from Bangladesh and 217 from Malaysia) in the study completed a structured questionnaire. The results reveal that self-medication was significantly more prevalent among Bangladeshi students (76.34%) compared to Malaysian students (39.2%). Financial barriers, lack of awareness, and difficulty in accessing healthcare services were the main drivers of self-medication in Bangladesh, while in Malaysia, peer influence and convenience were the primary reasons. The study highlights the importance of targeted interventions to raise awareness about the risks of self-medication and to improve healthcare access for students.