Background <p>Periodontal disease exhibits bidirectional associations with autoimmune diseases; however, comprehensive histological, radiographic, and correlational differences in periodontal tissues between patients with varying immune statuses remain poorly characterized.</p> Objective <p>To compare inflammatory cell infiltration patterns, junctional epithelium characteristics, radiographic findings, and clinical-histological correlations in periodontal tissues between patients with periodontitis and concurrent autoimmune diseases versus those with periodontitis alone.</p> Methods <p>A cross-sectional study was conducted on 40 participants: 20 with periodontitis and autoimmune diseases (rheumatoid arthritis, type 1 diabetes, systemic lupus erythematosus, asthma) and 20 with periodontitis without autoimmune diseases. Periodontal tissue biopsies were analyzed for inflammatory cell infiltration and junctional epithelium characteristics. radiographic parameters were quantified using standardized protocols. A correlation analysis was performed between clinical and histological parameters.</p> Results <p>The autoimmune group showed significantly higher inflammatory cell infiltration (36% higher total cell density, <i>p</i> = 0.001), reduced junctional epithelium thickness (185.4 ± 28.7 vs. 242.8 ± 31.2&#xa0;μm, <i>p</i> = 0.001), and 32% more alveolar bone loss (<i>p</i> = 0.019). Strong correlations between clinical and histological parameters were observed in autoimmune patients (<i>r</i> = 0.65–0.78, <i>p</i> &lt; 0.05) but not in controls.</p> Conclusions <p>Patients with autoimmune diseases exhibit enhanced inflammatory cell infiltration, compromised integrity of the junctional epithelium, increased radiographic bone destruction, and altered clinical-histological relationships in periodontal tissues, suggesting a distinct clinical entity requiring specialized management.</p>