Clematis flammula L. (CF) (Ranunculaceae) is widely used traditionally by native Berber populations in Algeria to treat gastrointestinal disorders. The present study was conducted to assess the gastroprotective properties and the underlying mechanisms of CF leaves ethanolic extract (CFEE) in four ulcer models in mice. After total phenol quantification, the gastro-protective effect of the CFEE was evaluated by macroscopic and microscopic analyses, investigation of antioxidant (superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and pro-oxidant (malondialdehyde (MDA)) parameters. Furthermore, the impact of CFEE pre-treatment on mucus level, myeloperoxidase (MPO) and gastric proton pump (H+/K+-ATPase) activities was determined. Pro-kinetic properties were also assessed.Pharmacological investigation of CFEE showed a dose-dependent gastro-protective potential in different ulceration models, in close correlation with its high antioxidant activity (SOD, CAT and GSH). The most interesting underlying mechanisms were a remarkable reduction of MPO and proton pump activities (90 and 99% inhibition, respectively). Histological examination confirmed the preventive action of CFEE against offensive agents associated with increased mucus production and reduced gastric emptying and intestinal motility.Our findings provide a scientific basis for the ethno-pharmacological purpose of the studied plant.