Pernicious anemia, historically tied to vitamin B12 malabsorption due to intrinsic factor secretion impairment, has evolved in understanding, especially concerning its association with autoimmune gastritis. This systematic review dives deep into the multifaceted relationship between Helicobacter pylori (H. pylori) infection, autoimmune gastritis, and the presence of anti-intrinsic factors and anti-parietal cell antibodies. Comprehensive database searches revealed a higher prevalence of H. pylori infection in pernicious anemia patients, with some studies suggesting a consequential increase in the aforementioned antibodies. Interestingly, eradication of H. pylori displayed potential therapeutic effects; patients showcased reductions in antibody titers, improved histopathological findings, and reversion of atrophic changes in gastric corpus. Such outcomes highlight the conceivable benefits of considering H. pylori infection during the evaluation and management of pernicious anemia and autoimmune gastritis. However, disparities across studies make direct comparisons challenging. It's essential to approach the potential role of H. pylori in these conditions with caution. Further research is warranted to cement conclusions and refine clinical management strategies. This review seeks to prompt new investigative avenues into the intricate link between H. pylori, autoimmune gastritis, and pernicious anemia, ultimately enhancing patient care.