Background: Despite all their benefits, improper use of medicines can bring potential health hazards. Though it was previously considered unnecessary, responsible self-medication is regarded as an essential aspect of self-care. Objectives: To explore the Knowledge, Attitude, and Practice on Over-the-Counter Drugs (OTC) use, and its determinants among the adult population in Jeddah, Saudi Arabia Method: It was a cross sectional study, where data were collected through online Google form to collect information on 503 subjects; where the sample type was a convenient one. A predesigned questionnaire was used to collect information on personal, sociodemographic and clinical information, as well as on the knowledge, attitude and practice on use of OTC drugs. Statistical analysis: SPSS version 24 was used, and the Subroutine Chi square test of significance was used. The level of significance was 0.05. Results: The majority of the enrolled subjects (83.3%) used OTC drugs (419/503). About 60% were under the age of 40 years old. Lower educational level, and increased salary over 10,000 SR were significantly associated with the use of OTC drugs (p < 0.05). About 80% were advised on the use of the OTC drugs by pharmacists; and 53.7% read about indications, side effects and contraindications of the OTC drugs before their use. About 80% used them for emergency; and 71% used them for treatment of mild illnesses. About 90% used them because of their past experience with their use, and 30% used them to avoid consultation fees. Painkillers were used by 97.4% of the subjects; in addition, cough suppressants (71.8%), dietary supplements (69.2%), antihistamine (40.3%) and digestive and laxative drugs (48.9%) were used. About 30%, considered that OTC drugs were cheaper and convenient. About 45% of the subjects considered that OTC drugs were safe and effective. About 80% considered it was wrong. to use the OTC drugs with other medications Conclusion: In Saudi Arabia, OTC medications can easily be obtained at pharmacies for the purpose of self-treatment. Approximately 83% of Jeddah survey respondents reported that they had used OTC drugs. The most commonly used OTC medications were antipyretics, analgesics and anti-inflammatory drugs, and these drugs were more commonly used by respondents aged <40 years than those aged 40 years. The awareness level of the survey respondents on the side effects resulting from the use of OTC medications was relatively low. Keywords: OTC drugs, KAP, Saudi Arabia, mild illnesses