Objectives: The use of non-steroidal anti-inflammatory drugs (NSAIDs) is a rising problem in the modern medical world. NSAIDs are easily available over the counter and accessible to the public. As such, we have seen a need to assess the knowledge and perception of public use of NSAIDs. In this study, we aimed to explore the knowledge of public use of NSAIDs among the participants from major metropolitan areas in the Kingdom of Saudi Arabia. Methodology: This is a cross-sectional study conducted for a period of 6 months using a questionnaire, which was developed to evaluate the use of NSAIDs in several major metropolitan areas among the Kingdom of Saudi Arabia. This questionnaire was randomly distributed digitally using the Survey Monkey system to individuals in the Kingdom of Saudi Arabia via social networking sites. The survey collected demographic data, age, education, socioeconomic status. The patient knowledge about the administration of NSAIDs status with meals, side effects, expiry date, resource information and related knowledge issues. The data were tabulated and analyzed by using SPSS version 13. Results: In this study, a total of 3000 patients received the questionnaire and of them, 500 responded, which means the response rate was 16.6%. The highest percentage of responders were in the age group of 40 years and above (52.63% n=263). Majority of the responders were those who had a university degree (66.20% (n=329)). According to our results, 63.31% (n=316) of the participants they knew how to take NSAIDs, i.e. with or without food is essential. Approximately 45% (n=224) of the participants knew about the possible side effects of NSAIDs. Half of the study population thought that expiry date is the time by which drugs become ineffective, whereas 33.81% (n=169) of the participants thought that drugs become toxic after this time. Around 61.87% (n=309) of the participants obtained information about NSAIDs from the package insert, whereas 32.45% (n=162) of the participants obtained information from the internet. Conclusion: The primary knowledge regarding NSAIDs is inadequate in the Kingdom of Saudi Arabia. Patient education about NSAIDs is highly recommended at healthcare institutions to prevent drug-related mistake, reduce economic burden on the healthcare system in Saudi Arabia.