Esomeprazole is a proton pump inhibitor (PPIs) successfully used to inhibit gastric acid secretion and treat peptic ulcers and other acid-related disorders. However, the studies of the effect of esomeprazole on liver enzymes are limited. This study aims to investigate the effect of esomeprazole on liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphates (ALP) in peptic ulcer patients. Twenty-nine omeprazole users and twenty-four health control were recruited from outpatient clinics. Serum levels of liver enzymes Alanine transferase (ALT), aspartate transferase (AST), and alkaline phosphates (ALP) were evaluated at least 2 months after the medication use. Serum levels of ALP (74.31± 19.63 U/L, P<0.0001) were significantly higher in esomeprazole users compared to non-users. While serum levels of ALT (16.07± 6.3 U/L, P=0.008) were significantly lower in esomeprazole users. Serum AST levels (18.86±6.4 U/L, p= 0.192) were not changed between the 2 groups. Whilst this study did not confirm the hepatotoxicity of esomeprazole on the liver, it could indicate that esomeprazole might affect the liver. Further research is required to determine whether esomeprazole is hepatotoxic or not.