Peptic ulcer disease (PUD) and post-procedural artificial ulcers are common ulcer disease. For them, Proton pump inhibitor (PPI) and potassium-competitive acid blocker (P-CAB) are commonly used in clinical practice. PPI requires acid, time, and multiple doses, but P-CAB has fewer limitations. We compared the efficacy, safety and prevention of PPI and P-CAB in PUD and artificial ulcer. We searched PubMed, ClinicalTrials.gov, Embase, Cochrane Library, and Web of Science databases for all studies. All eligible randomized controlled trials up to August 5, 2023 were included. Healing rates, shrinking rates, treatment-emergent adverse events rates and recurrence rates were measured. Risk of bias, sensitivity analyses, and heterogeneity were also performed. 20 researches which were selected from 926 screening studies and in total 6567 participants were included. The risk ratio (RR) of healing rate with P-CABs versus PPIs of PUD at 4-week was RR 1.01 (95% CI 0.98-1.04). In addition, the healing rate distinction of artificial peptic ulcer was RR 1.04 (0.89-1.22), and the shrinking rate was MD 0.10 (-1.30-1.51). The result of TEAEs rate of PUD was RR 1.11 (0.91-1.35) and the delayed bleeding rate of artificial ulcer was RR 0.35 (0.16-0.80). The RR for recurrence rate of drug-related ulcers was 0.45 (0.25-0.81). P-CAB is non-inferior in healing artificial ulcer and conventional PUD, also the incidence of TEAEs. But there may be a statistical advantage in holding back delayed bleeding and preventing drug-induced ulcers. More standardized experiments are needed for further applications and more precise conclusions.