Objective: This study aimed to investigate the protective role of licorice on indomethacin-induced gastric ulcer in male albino rats compared to anti-ulcer drug; ranitidine. Methods: Fifty male adult rats were randomly allocated into five groups (10 rats/each); control, licorice, indomethacin, licorice/indomethacin, and ranitidine/indomethacin treated groups. Serum, gastric juice, and gastric tissues were collected for biochemical and histopathological analysis. Results: The obtained results revealed that licorice pre-treatment showed potent anti-ulcerative effect as; volume and total acidity of gastric secretion were markedly decreased, attenuated the severity of gastric lesion as confirmed by PM and histopathological examination showed preservation of gastric epithelium and ulcer healing. Moreover, gastric ulcer score, gastric MDA, and serum IL-6 were obviously decreased along with increased gastric GSH, CAT activity and NO. Interestingly licorice had no side effects on the liver and kidney evidenced by increased serum total protein, and albumin besides declined the activities of serum aminotransferases without significant changes in the serum urea, uric acid, sodium, potassium, and chloride levels. Conclusion: It was concluded that the used dose of licorice showed potent anti-ulcerative activity and more safer on the liver and kidney functions compared to the standard commercial drug; ranitidine.