Background: Stomach ulcer is one of the diseases that many patients suffer from all over the world, and it causes damage to the intestinal wall. Some research has shown that Bauhinia thonningii extract, which has been traditionally used to treat a variety of ailments, including stomach ulcers, has powerful antioxidant and mucus-increasing properties. Objective:This research is aimed at studying the mechanism(s) through which methanolic (MBST) and chloroform (CBST) extracts of B. thonningii stem bark protects against ethanol-induced stomach damage in rats. Material and Methods: MBST and CBST were evaluated in vivo for their cytoprotective qualities employing stomach acidity, mucus content, macroscopic and microscopic methods, lipid peroxidation, nitric oxide, mass spectroscopy, 2D gel electrophoresis, and biochemical indicators. These extracts were tested in vitro on lipopolysaccharide/interferon-stimulated rat cells. Additionally, in-vivo, and in-vitro toxicity investigations were conducted. FRAP, DPPH, and ORAC tests were used to determine the antioxidant activity of MBST and CBST. Chemical and spectroscopic approaches were used to analyze the phytochemistry of MBST and CBST.Results: The gross and histological characteristics of B. thonningii proved its anti-ulcerogenic effects. MBST has gastroprotective effects by modulating lipid peroxidation and proteomics indicators [heat shock protein (Hsp60), disulfide isomerase (ERp60), protein disulfide-isomerase, creatine kinase B, cytosolic malate dehydrogenase, peroxiredoxin-6, and ATP synthase]. MBST and CBST have substantial impacts on nitric oxide both in-vitro and in-vivo. In comparison to CBST, methanolic extract (MBST) demonstrated greater gastroprotective properties, polyphenolic content, and antioxidant activity. The plant extracts did not show any toxicity in-vitro or in-vivo. MBST shows anti-ulcer action, which may be ascribed to its ability to reduce ethanol-triggered oxidative injury, to intervene in proteomic mechanisms, and to modulate nitric oxide.Conclusion:The present study found that stem bark extracts of Bauhinia thonningii Schum have cytoprotective activities against in vivo ethanol-induced damage due to its powerful antioxidant and mucus-increasing capabilities. Bauhinia thonningii warrants more attention since it may provide an exciting novel medication for the treatment of acute erosive gastropathy.Keywords: Bauhinia thonningii Schum;polar and non-polar extraction; peptic ulcer; nitric oxide; proteomics