Helicobacter pylori (H. pylori) infection is a primary pathogen responsible for gastrointestinal diseases, including gastritis, peptic ulcer disease, and gastric cancer. Therefore, the eradication of H. pylori is crucial for the prevention and treatment of these conditions. However, the increasing antibiotic resistance has led to a gradual decline in the efficacy of traditional Proton Pump Inhibitors (PPIs) in triple or quadruple therapy, posing new challenges for H. pylori eradication. Potassium-competitive acid blockers (P-CAB) represent a novel class of acid-suppressing drugs that exert potent and sustained acid suppression by competitively inhibiting the potassium-binding site of the H+/K+-ATPase. Compared to traditional PPI, P-CAB offers advantages such as rapid onset of action, prolonged duration of effect, and less susceptibility to the influence of CYP2C19 genetic polymorphism, highlighting their significant potential in H. pylori eradication therapy. This article aims to comprehensively review the clinical efficacy and safety of P-CAB-containing regimens in first-line and rescue treatments for H. pylori eradication. This includes but is not limited to dual therapy combining P-CAB with other antibacterial agents, triple therapy, and quadruple therapy in combination with bismuth. By analyzing existing clinical research data, we will explore the application effects of P-CAB in different treatment regimens, as well as the advantages and potential limitations compared with PPI. Additionally, this article will focus on the tolerability of these treatment regimens in patients and the incidence of adverse reactions, to provide scientific evidence and new perspectives for clinicians in selecting appropriate H. pylori eradication regimens.