Abstract: Objective To analyze the value of peripheral blood interleukin-18 (IL-18), NOD-like receptor protein 6 (NLRP-6), erythrocyte sedimentation rate (ESR), and C reactive protein (CRP) levels in assessing disease severity and treatment efficacy in elderly patients with ulcerative colitis (UC). Methods A total of 100 elderly UC patients admitted to Changsha Hospital of Traditional Chinese Medicine from November 2020 to December 2023 were enrolled. They were categorized into mild, moderate, and severe groups based on disease severity, and into treatment-responsive and treatment-nonresponsive groups based on therapeutic outcome. Differences in peripheral blood IL-18, NLRP-6, ESR, and CRP levels before and after treatment were compared among the groups. The cut-off values and efficacy of these indicators for assessing disease severity and predicting treatment response were analyzed. Results Among the 100 elderly UC patients, 19 were mild, 34 were moderate, and 47 were severe; 71 patients were assigned to the treatment-responsive group after therapy. The moderate group showed higher IL-18, ESR, and CRP levels but lower NLRP-6 mRNA expression than the mild group (P ＜ 0.05). The severe group exhibited higher IL-18, ESR, and CRP levels and lower NLRP-6 mRNA expression than the moderate group (P ＜ 0.05). In the treatmentresponsive group, IL-18, ESR, and CRP levels before and after treatment were lower than the treatment-nonresponsive group, while NLRP-6 mRNA expression was higher than the treatment-nonresponsive group (P ＜ 0.05). ROC curve analysis showed that the combination of all indicators before treatment yielded an AUC of 0.860 for assessing disease severity, with sensitivity and specificity of 0.868 and 0.851, respectively; the combination for predicting treatment efficacy had an AUC of 0.840, with sensitivity and specificity of 0.830 and 0.851, respectively. Conclusion Disease progression in elderly UC patients is associated with increased peripheral blood levels of IL-18, ESR, and CRP and decreased NLRP-6 mRNA expression. Moreover, higher peripheral blood IL-18, ESR, and CRP levels, and lower NLRP-6 mRNA expression are associated with limited therapeutic benefit from mesalazine combined with bifidobacterium triple viable capsule therapy.