The objective of the present study was to investigate the knowledge and practices concerning unused and expired medicine among pharmacy and nursing students at King Saud University, Riyadh, Saudi Arabia. A cross-sectional study design was used. The study used a validated paper-based, self-administered questionnaire. Statistical analyses were performed using SPSS, Version 24. The response rate was 70.4% (n = 352). The results indicated that 57.4% of pharmacy students and 53.4% of nursing students check the expiry date of medicine before procuring, and 37.6% of pharmacy students and 52.5% of nursing students keep unused medicine until it expires. With regard to disposal, 78.9% of pharmacy students and 80.5% of nursing students reported discarding expired medicine in household garbage or flushing it down a sink or toilet. Only a small percentage returns leftover medicine to a medical store. There was a statistically significant difference between pharmacy and nursing students in regard to checking the expiry date of medicine before procuring (p = 0.01), and keeping unused medicine until it expires (p = 0.03). The study concluded that the majority of respondents dispose of medicine unsafely. The findings suggest that creating awareness regarding proper medicine disposal procedures among university health care students in Saudi Arabia is needed.