The present study investigated the therapeutic effects of Chromolaena odorata leaf extract on aspirin-induced gastric ulcers in rat models. The phytochemical constituents of the extract were analyzed using GC-MS, and its functional groups were studied using FTIR. Acute toxicity tests were performed to assess its safety profile. Albino rats were divided into six groups, receiving different pre-treatments before ulcer induction, while a separate set of rats underwent acute toxicity testing. After ulcer induction, various physiological and biochemical parameters were evaluated to assess the extract's impact. Enzyme activity, pro-inflammatory cytokines, hematological parameters, and serum total protein were also analyzed. Histological examination provided insights into the extract's effects on ulcer healing. The results indicated low toxicity at lower doses of the extract but mild toxicity at higher doses. The extract exhibited dose-dependent inhibition of ulcers, with the highest dose showing the greatest effect. It also regulated various parameters related to gastric mucosal health, antioxidant enzyme expression, and inflammation. Histological examination revealed varying degrees of restoration and inflammation, suggesting the extract's potential in promoting epithelial restoration. Overall, the study suggests that Chromolaena odorata leaf extract has therapeutic potential in managing gastric ulcers by promoting tissue repair, reducing inflammation, and inhibiting ulcer formation. Further research is needed to explore the underlying mechanisms and validate its efficacy in clinical settings.