Self-medication involves using drugs, herbs, or remedies on personal initiative or advice without seeking advice or guidance from a health care professional. One issue affecting the health system is the Self-medication use of antibiotics. This study aims to assess the knowledge and awareness level of antibiotic resistance resulting from self-medication use among populations in KSA. This observational study was conducted in KSA; the data gatherers created an online questionnaire to gather information from randomly selected Saudi Arabian patients. The Statistical Package of Social-Science Software (SPSS) application, version 20, was then brought in the data. To go through statistical analysis. The study included 1,071 participants; the majority of respondents were between 20 and 40 years old. The data indicates a slightly higher representation of females (58.7%) compared to males (41.3%). The majority of the group, 75.3%, have a low level of knowledge on the topic, while 19.5% have a medium level, and only 5.2% have a good level of knowledge. There is a lack of awareness of antibiotic resistance resulting from self-medication. Knowledge and awareness scores were significantly associated with the occupation and monthly income of participants. The knowledge and awareness level of antibiotic resistance resulting from self-medication is a pressing issue that needs to be addressed urgently. The lack of understanding about appropriate antibiotic use, combined with unrestricted access to antibiotics and the proliferation of inaccurate information, contributes to the development of antibiotic resistance.