The researcher isolated and identified eight active metabolites from the native plant Tamarix aphylla and studied the medicinal activity of the extract toward gastric ulcers applying in-vivo experiments using albino rats animal model and used the computerized chemical methods; protein-protein interaction and network pharmacology. This study highlighted the significance of using T. aphylla leaves crude extract as an anti-gastric ulcer candidate. Our findings have illuminated the potent anti-inflammatory and antioxidant effects of T. aphylla, which are likely mediated by suppressing IL-1β, IL-6, TNF-α, and MAPK signaling pathways, without compromising gastric acidity. our study has revealed the remarkable potential of T. aphylla crude extract in significantly ameliorating gastric ulcers induced by indomethacin administration. Our findings provide compelling evidence that the therapeutic efficacy of the extract can be attributed to its ability to downregulate the MAPK signaling pathway, and to its potent antioxidant effects, without compromising gastric acidity. In light of these results, T. aphylla leaf extract offers a promising and effective therapy for the treatment of inflammation and NSAID-induced gastric ulcers, while also providing a safer alternative to traditional antisecretory drugs with their notorious side effects.