Peptic ulcer (PU) is a major health hazard. Ulceration of non-steroidal anti-inflammatory drugs (NSAIDs) has been considered a major health hazard. Several pharmaceutical products have been engaged to protect and treat NSAIDs- induced PU, but there was the incidence of relapses, and many severe side effects were produced during ulcer treatment. Recently, there has been a growing interest in medicinal plants. Ficus carica L. leaves’ extract (FCLE) has had many biological activities. The present work aimed to evaluate the possible protective utility of FCLE against NSAIDs-induced PU in rats. The PU was induced by interperitoneal (i.p.) injection of indomthacin (IND) (30 mg/kg), while FCLE was given to rats by oral gavage at the dose of 500 mg/ kg, and ranitidine (RNA) was used as a reference drug (50 mg/kg) for 3 weeks before IND injection. Gastric mucosal lesions index (UI) was determined. Total acid outputs (TGA) and pH were assessed in gastric juice. Gastric mucosal malondialdehyde and catalase levels were determined. Gastric prostaglandin E2 (PGE2) and nitric oxide (NO), as well as serum pro- inflammatory cytokines were detected. Histopathological examination for gastric was carried out. There was a significant elevation (P< 0.001) in UI, TGA, pepsin , gastric oxidative stress and inflammation along with a significant decline in gastric pH, mucin, PGE2 and NO levels in the PU group compared with the pretreatment PU groups with FCLE, RAN and FCLE+RAN. Moreover, there was a noticeable improvement in the gross structure and histopathological results of the pretreated PU groups compared with PU group. The most effective pretreatment was seen in the PU group co-pretreated with FCLE+ RAN. These protective effects could be explained via the enhanced gastric protective factors, stimulated antioxidant status, and diminished pro-inflammatory cytokines.