To assess the knowledge, attitude, and practice of antibiotics (ABs) use and misuse among adults living in Riyadh, Saudi Arabia. Methods: In this cross-sectional study, a self-administered questionnaire was distributed to participants from  March 2016 to January 2017 in the outpatient department of King Khalid University Hospital and Dental Hospital, King Saud University, Riyadh, Saudi Arabia. The questionnaire was divided into 4 sections. The first and second section inquired regarding demographic details and knowledge of ABs. The third section assessed practice of ABs and the fourth section assessed attitude of participants towards ABs use. Questionnaires were hand delivered to respondents using convenience sampling. Statistical analysis using frequency distributions and knowledge responses of AB resistance for 'yes' and 'no' were associated with participant characteristics using Chi-square test.  Results: A total of 1966 questionnaires were completed (response rate: 93.5%). Sixty-seven percent of the respondents were unaware of the meaning of ABs resistance. Sixty-seven percent of respondents were unaware of ABs being harmful for children's teeth and 64.9% unaware of ABs that develop allergy and death.  Twenty-four percent believed that ABs worked on viruses, 31% on cold and 21% can cure cough. Almost 51% used ABs without physician prescription while 37.5% obtained ABs directly from pharmacists without physician's prescription. Almost 42% participants discontinued ABs on alleviation of symptoms. There was significant difference in knowledge response of AB resistance and source of AB use (p=0.026), reason of AB use (p=0.038) and discontinuation of ABs (p=0.041). Conclusion: Adults showed insufficient knowledge and understanding regarding the safe use of ABs consumption among the population.