(1) Background: It is crucial to provide safe and knowledgeable healthcare practices because no research has been performed 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, whereas 229 (57.39%) were female. Gender, occupation, and marital status showed non-significant associations except for menstrual cycle and joint pain, where marital status displayed significant associations (p > 0.001). Education and monthly income exhibited non-significant associations for all these 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. Meanwhile, >50% of the participants had knowledge of adverse events related to the use of NSAIDs, whereas 25% had no knowledge. Moreover, 59 (25.76%) participants reported discomfort with the use of NSAIDs. In addition, 50% and >75% of respondents believed that NSAIDs could induce peptic ulcers and kidney damage, respectively. (4) Conclusions: This study shed light on the knowledge and patterns of NSAIDs use in the population of Hail, Saudi Arabia. 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.