Background: Sesbania grandiflora are characterized by their high anti-oxidant properties. The degeneration of neurons in Alzheimer disease mainly occurs because of high production of free radicals. However, the impact of Sesbania grandiflora on cholinergic system and oxidative stress parameter has not been investigated. Aim: The present study was designed to evaluate the neuroprotective effect of ethanolic extract of Sesbania grandiflora seeds in mice. Material and method: The seeds of Sesbania grandiflora were powdered and subjected to successive extraction in Soxhlet apparatus. The different doses of ethanolic extract of Sesbania grandiflora seeds were evaluated for its neuroprotective activity against celecoxib induced amnesia in mice. Result and Conclusion: Phytochemical analysis of various extracts of Sesbania grandiflora revealed the presence of steroid, saponin, flavonoid, tannins and phenolic compounds. The ethanolic extract of Sesbania grandiflora significantly improves the memory of mice and reestablishes the amnesia induced by celecoxib. In addition to improvement in memory the extract treatment also decreases the activity of AchE and MDA and restore the antioxidant anzyme SOD, GSH and catalase in experimental animals. The results of our study showed that ethanolic extract of Sesbania grandiflora improve the cognition dysfunction in celecoxib treated mice through the modification in cholinergic system or by the blockage of oxidative stress and inhibition of AchE enzyme.