The irrational use of medicines remains prevalent globally despite education efforts, leading to decreased treatment quality and increased healthcare costs. With the rise of online learning during the COVID-19 pandemic, virtual simulation offers a promising solution to enhance the teaching of rational medicine use among medical students. This study aimed to investigate medical students' perspectives and needs regarding the implementation of virtual simulation in learning the rational use of medicines. This study, conducted at Universitas Indonesia from August 2022 to September 2023, used a mixed-method approach to assess the needs for developing virtual simulation in education of rational medicine use. A validated questionnaire with 14 closed-ended and 14 open-ended questions was completed by 281 medical students. The quantitative data were analysed descriptively, using SPSS v16, while thematic analysis was applied to open-ended responses. Students perceived virtual simulations to be the most effective tool for distance learning and suggested features like case scenarios, realistic representation, a good user interface, and user-friendly navigation. The majority preferred a 10-20-minute duration for virtual simulations. Additionally, 52.3% had no prior knowledge of the rational use of medicines, but acknowledged its importance. Virtual simulations could be used to explain the concept, management, and implementation of the rational use of medicines. Virtual simulation should be implemented in distance learning on rational medicine use to increase students' motivation, understanding, retention, interactivity, and focus. The findings might be utilized by medical educators to tailor virtual simulation design to meet medical students' needs and expectations.