Self-medication can potentially do well and also harm people. It is a common practice and internationally has been reported as being on the rise. Studies have observed self-medication as a common practice among group of health workers that included dental, midwifery and nursing students. Hence, this study assessed the knowledge and practice of self-medication among students of school of nursing in selected schools in Osun State. It was a descriptive cross-sectional survey. Samples of two hundred nursing students were included in the study using purposive sampling.The result in this study showed that majority (91%) of the nursing students had high level of knowledge and about two third (64.5%) indulge in high practice of self medication respectively. More than half of them signified that presence of minor ailments and having enough knowledge about drugs were the factors that always make them to self-medicate, while more than forty percent indicated that financial constraint, previous experience, time saving, advertisement and unavailability of health care services as factors that sometimes influence self-medication. Significant relationship existed between knowledge and practice of self medication (t = -3.116, df = 198, P < 0.05).Nursing students demonstrated high level of knowledge about medication and its effects. Majority indulge in self-medication practices. Those with high level of knowledge practice of self medication less. It would be safer if those who self-medicate have sufficient knowledge to prevent serious effects. It is recommended that policies be formulated to control the purchase and use drugs.