Background: In traditional folk medicine, Limonium tetragonum is used in the treatment of uterine hemorrhage, tinnitus, and oligomenorrhea. Objective: This study aimed to identify the therapeutic effect of L. tetragonum EtOAc extract (EALT) on liver of mice with chronic alcohol poisoning. Materials and Methods: C57BL/6J mice were administered 100 mg/kg of EALT with a single binge ethanol/Lieber-DeCarli liquid diet for 8 weeks. Results: The chronic-binge ethanol diet induced a significant increase in liver marker enzyme activities. Coadministration of EALT reversed the elevation of serum total cholesterol and triglyceride as well as aspartate aminotransferase and alanine aminotransferase due to chronic alcohol consumption. Histologic findings including markedly attenuated fat accumulation in hepatocytes were observed in EALT-treated mice. EALT supplementation prevented alcoholic liver injury through attenuation of inflammatory mediators such as toll-like receptor-4, cytochrome P4502E1, and cyclooxygenase-2, and inflammatory cytokine interleukin-6. Conclusion: Results provided direct experimental evidence for the hepatoprotective effect of EALT in the NIAAA mouse model. Therapeutic attempts with the L. tetragonum extract might be useful in the management of alcoholic liver disease.