Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) and caffeine-containing beverages are widely consumed but their impact on gastrointestinal (GI) health requires further investigation. This cross-sectional study investigated the relationship between NSAIDs use, caffeinated drink consumption, and the prevalence of self-reported GI symptoms in a Jordanian subpopulation. Methods: An online survey was administered to 400 Jordanian individuals aged 18-65 years. Data on sociodemographics, NSAIDs use, caffeine consumption, peptic ulcer disease (PUD) history, and GI symptoms were collected. Contingency tables were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between exposures and outcomes. Results: The prevalence of self-reported PUD-related GI symptoms was 6.0%. NSAID users had higher odds of PUD (OR = 2.431) and related GI symptoms, including abdominal pain (OR = 4.688, p < 0.001) and discomfort (OR = 8.068, p < 0.001). Caffeine consumption was associated with self-reported burning stomach pain (OR = 14.104, p < 0.001), fullness (OR = 8.304, p = 0.010), and bloating (OR = 8.304, p = 0.010). Coffee, tea, soft drinks, and energy drinks were associated with increased odds of various GI symptoms (ORs 2.018-12.715, p < 0.05). Conclusions: NSAIDs use and caffeine consumption were independently associated with the increased prevalence of self-reported PUD and related GI symptoms. Despite the lack of adjustment for necessary confounders, our findings highlight the importance of considering the potential GI effects of NSAIDs and caffeine. Public health strategies promoting their safe use may help reduce the burden of GI disorders.