Background: Medications are not only used for disease treatment, but also for diagnosis and prevention of the disease. Not all the prescribed drugs are used by the patients, due to lack of adherence to therapy, there are chances of stocking up the unused or expired drugs at home. It is important to provide practical and scientific guidelines for the safe disposal of expired, unused, and leftover medications. Most developing countries lack standard guidelines for the safe disposal of expired, unused, and leftover medications. There are very few studies conducted in this region to assess the knowledge of the safe disposal of unused drugs. Aims and Objectives: The present study was undertaken to assess the knowledge, attitude, and practice of disposal of unused or expired medications. Materials and Methods: This was cross-sectional, questionnaire-based study conducted among 2nd year undergraduate medical students at a Medical College in South India. The questionnaire included three parts: Part I includes demographic details of the students and questions on knowledge of safe disposal of expire/unused drugs, Part II includes questions on attitude towards the safe disposal of expired/unused drugs, and Part III includes questions on practices toward the safe disposal of expired/unused drugs. The responses received from the participant was analyzed using Microsoft Excel (2019 version), and the results are explained in frequency and percentage. Results: A total of 118 2nd year medical undergraduate students participated in the present study. Out of 118, 62 (52.5%) were female students and 56 (47.4%) were male students. Among all the participants, 98 (83%) of students said that they are aware of medicinal waste. In the present study, 73 (61.8%) students knew about the safe disposal of unused, expired, and leftover medications. Most of the students (93.2%), agreed that unsafe disposal of unused, expired, and leftover medications would adversely affect the environmental, animal as well as human health. And 50% of the students, strongly agreed that educational activities like drug take-back programs should be introduced among the public people. When the students were asked about their practice of keeping expired, unused, or left-over drugs at home, 66.1% (78) of the students said yes and 47.2% (40) of the students said they do not keep the leftover medicine at home. Topical formulations (63.5%) were the most common group of drugs that were stored. The majority of students (73%) reported that they would throw unused/expired medications in dust bins at home. Self-discontinuation is most the common reason for storing drugs in the majority of the study participants (39%). Conclusion: In the present study, the 2nd-year medical undergraduate students had awareness regarding the harmful events associated with improper disposal of unused or expired drugs. But due to lack of information or knowledge of safer methods available, majority of the students were following inappropriate methods for disposing leftover or expired medication at home. Indian Government should provide national level guidelines and conduct awareness programs, mediated through healthcare professionals to bring significant changes about the disposal of unused or expired medications.