OBJECTIVES: This study was conducted to evaluate the  knowledge and awareness of medicines use among general public; and to find out  the factors influencing medicine knowledge. METHODS: A cross-sectional survey was conducted using self-administered questionnaire among the general public in Penang, Malaysia. Adult aged 18 years old and above were invited to participate in this survey. A convenience sampling method was used to recruit the respondents from the household level. RESULTS: Out of a maximum score of 10 points of knowledge, the mean score was 6.45±2.43 indicating a moderate knowledge of medicines use. The high score of knowledge was significantly associated with females, older age group and Malays (p<0.05). Furthermore, high education level and high monthly income were significantly influenced peoples knowledge about medicines use. This study showed that more than half of the respondents (51.5%)  were not aware about the generic and brand names of medicines. Moreover, 46.4% of them didn’t know that the overuse of vitamins can cause negative effects and the overuse of paracetamol will lead to liver toxicity (29.1%). More than 40% didn’t know that storing ointments and syrups in the refrigerator will not extend the expiration date. In addition, 31.2% of the respondents were not aware that some modern and traditional medicines cannot be taken together and 47.9% of them believed that medicines registered in Malaysia are safe to use without any side effects. CONCLUSIONS: This study showed that the general public have limited knowledge and awareness regarding some aspects of using medicines. Educational intervention programs are needed to increase the knowledge and awareness of medicines use among general public. In addition, the health care authorities can help to create better strategies in order to promote the rational use of medicines in the overall population.