In the present study, the gastroprotective mechanism of aqueous extract of Piper nigrum and Ferula foetida (AEPF) was investigated. In the current study AEPF showed significant anti ulcer activity in rats. The antiulcerogenic impact of the AEPF is also associated with its antisecretory action since acid may be a major consideration of the event of ulceration. The current data also clearly demonstrated that 400 mg/kg is more effective than 200 mg/kg and 100 mg/kg dose of AEPF and has shown increased pH and decreased total acidity of gastric fluid. The ulcerogenic effect of cysteamine-induced duodenal ulcers was developed in rats that received cysteamine HCl 400 mg/kg. The exact mechanism of pathological process within the cysteamine-induced peptic ulcer model is not totally known, but hypersecretion of gastric acid, deterioration of mucosal resistance, and promotion of gastric emptying are among the possible mechanisms. In cold restraint stress-induced ulcer model, blood parameters such as glucose, cholesterol, and triglycerides were estimated. The significant increase in blood sugar level was discovered because, beneath nerve-racking conditions, ductless gland secretes corticosterone in man and glucocorticoid in rats. AEPF significantly reduced the elevated serum cholesterol and triglycerides levels, which may be due to inhibition of stimulation of the sympathetic nervous system. Therefore, it could act as a potent therapeutic agent against peptic ulcer disease.