Since many researchers previously reported that M. tinctoria and V. negundo possess antiulcer activity thus the main objective of our study is to compare the antiulcer activity of both plants. Pharmacogenetic, phytochemical, and pharmacological assessments will be used to identify the antiulcer effect of the M. tinctoria and V. negundo. By using a vacuum rotary evaporator, M. tinctoria and V. negundo alcoholic extracts were prepared. The OECD criteria for acute toxicity and sub-acute oral toxicity were done for 14, 28 days. For antiulcer activity determination, in-vitro and in-vivo methods were used. In the Pylorus ligation-induced gastric ulcer model, 400mg/kg M. tinctoria was significantly different from the standard and revealed a 4.820±00** ulcer index, whereas 400mg/kg V.negundo revealed a 4.980±04*** ulcer index. At the dose of 400 mg/kg of M. tinctoria ulcer index observed 0.46 ± 0.02 and V.negundo was 0.49 ± 0.21 substantially reduced the effect of ulcers and the ulcer index observed in swimming stress-induced ulcers. M. tinctoria and V.negundo observed 4.1±0.37 and 4.5±0.19 ulcer index in NSAIDs-induced stomach ulcers in rats administered by oral route at the dose of 400 mg/kg. With an IC50 of 35 µg/ml, M. tinctoria significantly reduced ATP hydrolysis by goat stomach ATPase. For the positive control group, Omeprazole (10-50µg/ml) was used to lower Hydrogen Potassium ATPase activity, with an IC50 of 29 µg/ml. In comparison to V.negundo, pharmacological studies show that M. tinctoria extract (MTE) successfully protects the stomach mucosa from ulcers generated by different agents.