The study analyzed the relationship between Helicobacter pylori infection and inflammatory bowel disease (IBD) through a systematic review and meta-analysis of 44 studies with 14,100 IBD patients and 291,352 controls. The prevalence of H. pylori was significantly lower in IBD patients (13.48%) compared to controls (OR 0.45, 95% CI: 0.35–0.53, p < 0.01). The negative association was strongest in Crohn's disease (OR: 0.36, 95% CI: 0.28–0.45) and in the Eastern population (OR: 0.34, 95% CI: 0.26–0.40). The heterogeneity of the results was high (I² = 84.93%), but the sensitivity analysis confirmed the robustness of the findings. No publication bias was detected. A meta-analysis shows a significant negative association between H. pylori and IBD, and the bacterium may have an immunomodulatory role. The study is registered under CRD42024567688.