(1) Background: It is crucial to provide safe and knowledgeable healthcare practices because no research has been done on the knowledge and usage patterns of NSAIDs among the Hail population. (2) Method: Structured questionnaires were utilized to gather data from 399 individuals in Hail, Saudi Arabia for the cross-sectional analysis. The study assessed participants' knowledge regarding NSAIDs, patterns of use, reasons for use, and awareness of potential side effects. (3) Results: In the study, the gender distribution indicated that 170 participants (42.61%) were male, while 229 (57.39%) were female. Gender, occupation, and marital status showed non-significant associations (p>0.01), except for menstrual cycle and joint pain, where marital status displayed significant associations. Age had significant associations with muscle pain, menstrual cycle, and joint pain (p<0.01). Education and monthly income exhibited non-significant associations for all the reasons. The regression analysis demonstrated that gender played a significant role, with females having higher odds of knowledge (AOR = 1.75, 95% CI 1.10-2.88) than males. Age also had a notable impact, with individuals aged 50-59 (AOR = 0.21, 95% CI 0.07-0.66) exhibiting lower odds of knowledge. Education holding a Ph.D (AOR = 3.50, 95% CI 0.54-22.51) and business as an occupation (AOR = 6.12, 95% CI 1.10-35.10) had significantly higher odds of knowledge while housewives (AOR = 0.76, 95% CI 0.25-2.27) had lower odds. Meanwhile, >50% of the participants had knowledge of adverse events related to the use of NSAIDs while 25% had no knowledge. Moreover, 59 (25.766%) participants reported discomfort with the use of NSAIDs. In addition, 50% and >75% of participants’ considered NSAIDs can cause peptic ulcers and damage kidneys, respectively (4) Conclusions: This study shed light on the knowledge and patterns of NSAIDs use in the population of Hail, Saudi Arabia. While NSAIDs are commonly utilized for pain management, there exists a need for improved public awareness regarding potential risks and safe usage practices. Healthcare providers and policymakers should consider these insights to develop targeted educational initiatives and healthcare interventions to promote safe and informed NSAID utilization in the region.