Background: Aphthous ulcers (AU) and Rheumatoid Arthritis (RA) are conditions marked by inflammation, with Interleukin 8 (IL-8) playing a significant role in their pathogenesis. This study aims to evaluate the levels of IL-8 in saliva among individuals with AU, RA, both conditions and healthy controls, providing insights into its potential as a diagnostic biomarker and therapeutic target. Methods: The study, endorsed by the Ethics Committee of the University of Kufa, College of Dentistry, Department of Oral Pathology, employed a descriptive, analytical, and cross-sectional approach. Participants included patients with AU, RA, both conditions and a control group, totalling 94 individuals. Exclusion criteria encompassed medication use, other systemic conditions, and lifestyle factors like smoking. Saliva and blood samples were collected for IL-8 concentration measurement using ELISA and for Rheumatoid Factor (RF) and anti-CCP analysis. Results: Analysis showed the highest average salivary IL-8 levels in patients with both AU and RA (483.33 ± 141.20 pg/mL), followed by the RA group (338.57 ± 79.11 pg/mL), the AU group (381 ± 108.48 pg/mL), and the control group (213.69 ± 84.65 pg/mL). Significant differences in IL-8 levels were observed between these groups, with the combined AU and RA groups showing the highest concentrations. However, the variation in IL-8 levels between those who have both AU and RA and those with only RA was not statistically significant. Conclusion: The study highlights a distinct elevation in salivary IL-8 levels in patients with AU and RA, particularly in those suffering from both conditions.