Alzheimer's disease (AD) is a complex neurodegenerative disease affecting mental ability and neurocognitive functions. Crinum woodrowii Baker (C. woodrowii) is an endemic plant with significant ethnobotanical potential against neurological and inflammatory conditions with a characteristic improvement of cognitive functions.To assess the anti-AD potential of C. woodrowii extract through in-vitro assays and preclinical in-vivo screening and to validate its neuroprotective effect by biochemical and histopathological analysis.Herein, galantamine contents of the ethanolic extract of C. woodrowii were quantified using HPLC and LCMS. Further, the extract was examined for in-vitro cytotoxicity, anti-inflammatory, anti-cholinesterase activities, and in-vivo neuropharmacological studies.The extract exhibited low cytotoxicity on RAW 264.7 cells and the inhibition of LPS-induced nitric oxide production. The extract also showed anti-cholinesterase activities. The treatment with extract significantly rescued the rough eye phenotype in the Drosophila model of AD. In neuropharmacological screening, the extract showed no symptoms of acute oral toxicity in rats. The extract significantly reversed scopolamine-induced memory deficit in mice and improved their learning ability with memory retention in exteroceptive behavioral models. The pretreatment of mice with extract reinstated the elevated brain acetylcholinesterase, lipid peroxidation, and reduced glutathione levels due to scopolamine and aging. The extract also restored the altered superoxide dismutase and catalase levels. The extract alleviated neuronal tissue damage caused by the scopolamine, as indicated by the histological analyses of the brain.Our findings suggested that the C. woodrowii extract has neuroprotective properties and ameliorates cognitive dysfunction and hence could be explored further as a potential neurotherapeutics for treating AD.