Helicobacter pylori (H. pylori) is the most commonly identified cause of gastrointestinal (GI) infections, leading to disorders such as gastritis, ulcerative disorders, and gastric cancer. End-stage renal disease (ESRD) patients often experience GI symptoms as a characteristic of the uremic syndrome. H. pylori eradication therapy (ET) has been found to effectively relieve GI symptoms and prevent clinical complications in ESRD patients. Methods: We conducted a prospective cohort analytic hospital-based study on various Egyptian populations from November 2021 to December 2022. The study population comprised 80 ESRD patients who tested positive for H. pylori stool antigen (HpAS). The patients were divided into four equal groups, with each group receiving a different treatment regimen. The eradication of H. pylori was evaluated by HpSA one month after the end of ET. To evaluate the adequacy of hemodialysis (HD), we calculated and compared the Urea reduction ratio (URR) and Single-pool Kt/V (spKt/V) before and after ET. Results: The rate of improvement in GI symptoms after H. pylori eradication was 40%, 25%, 60%, and 55% in the four groups, respectively. The mean URR in the studied patients before ET was 65.13±2.46 and increased to 68.05±2.16 after ET (P value = 0.046). The mean Kt/V in the studied patients before ET was 1.32±0.08 and increased to 1.50±0.08 after ET (P value = 0.004). Conclusion: Eradication of H. pylori using quadruple and sequential treatment regimens can improve most GI symptoms. Our study concludes that H. pylori eradication significantly improves the efficacy of HD in ESRD patients.