Helicobacter pylori (H. pylori) infection constitutes a major pathogenic factor in gastric carcinogenesis and is extensively involved in tumor development, progression, and the modulation of the immune microenvironment. In recent years, immune checkpoint inhibitors (ICIs) have shown remarkable advancements in the treatment of advanced gastric cancer (GC). However, their efficacy varies markedly between patients. Emerging evidence indicates that the H. pylori infection status may profoundly affect treatment efficacy. Research has demonstrated that H. pylori regulates the PD-1/PD-L1 axis and anti-tumor immune responses through virulence factors (e.g., CagA and VacA) and alterations in the immune microenvironment. Additionally, infection-associated dysbiosis of the gut microbiota and suppression of T cell function are implicated in diminished ICI efficacy. Clinical data show that H. pylori-positive patients have markedly reduced overall survival (OS) and progression-free survival (PFS) compared with their negative counterparts after ICI therapy.This review summarizes recent advances in H. pylori infection and GC immunotherapy, and the underlying mechanisms, focusing on how H. pylori shapes the tumor immune landscape to impair ICI efficacy. Key molecular pathways, inflammatory cascades, and microbial interactions were also discussed. We evaluated the clinical utility of H. pylori status as a predictive biomarker, and explored combinatorial therapeutic strategies for infected patients. A deeper understanding of H. pylori-driven mechanisms and the development of precision medicine approaches hold promise for enhancing immunotherapy outcomes and offering novel therapeutic avenues for patients with GC.