Self-medication particularly with analgesics and antibiotics have been reported by WHO as one of the major causes of antibiotic resistance. In country, like Uganda there is a wide range of drugs, coupled with inadequate health services have resulted to an increased number of drugs used as a self-medication compared to prescribed drugs. Assessment of knowledge and practice of self-medication is needed especially in rural settings. This was an anonymous, questionnaire-based, descriptive study. Questionnaires containing closed ended questions were administered to 288 second year undergraduate medical students. Data analysis was performed using STATA 14. Descriptive statistics were performed in terms of frequencies and percentages. Statistical significance was assessed at alpha of 0.05. The research results indicated that the mean age was (24) and the majority of the students who participated in the study were male (63%). The prevalence of self-medication in the study was found to be markedly high (83.4%). The most important reason for self-medication was that it is cheaper (91%) and the majority (92%) of the students reported that they selfmedicated because of diarrhea/vomiting with antacids found to be the highly used class of drug (93%). Majority of the students got the information concerning the drugs through advertisements (98%) and (92%) of the students bought medicine from drug shops. In conclusion, most of the students feared having the side effects of the medications since they were self-prescribed without any experience. Keywords: Knowledge, attitude, practice, self-medication, undergraduate medical students, Uganda