Background: Phytotherapy is considered a complementary approach for preventing and treating many diseases. Plants are rich source of bioactive secondary metabolites of a wide variety such as saponins, tannins, terpenoids, alkaloids, and flavonoids. Sapindus laurifolia (fam: Sapindaceae), well known as soapnuts, are used medicinally as an expectorant, emetic, contraceptive, and for treatment of excessive salivation, epilepsy, chlorosis, and migraines. Objective: To isolation of fractions, estimation of total flavonoid content, in vitro antioxidant and in vivo neuroprotective activity of S. laurifolia fruit kernel. Materials and Methods: In this study, in vitro antioxidant activity is estimated by 2,2-diphenyl-1-picrylhydrazyl assay method. Neuroprotective activity is estimated by scopolamine-induced dementia method. In neuroprotective method, behavioral parameters were checked by escape latency (EL) time (s) by using the Morris water maze, active avoidance testing using elevated plus maze, and neurochemicals such as glutathione, catalase (CAT), superoxide dismutase (SOD), and Cholinesterase were estimated. Results: In scopolamine-induced dementia, increased EL time, active avoidance and neurochemicals such as glutathione, CAT, SOD and cholinesterase decreased. Whereas standard and Fraction S-treated animals decreased in EL time, active avoidance and increased locomotor activity, neurochemicals such as glutathione, CAT, SOD, and cholinesterase also increased. Conclusion: The present study clearly demonstrates that methanolic extract of S. laurifolia Fraction A (50 and 100 mg/kg) kernel significantly attenuate scopolamine-induced dementia by improving the learning, memory, antioxidant potentiality, and anti-acetyl cholinesterase activity. Therefore, this Fraction A can be a potential novel therapeutic strategy for controlling neurodegenerative dementia especially Alzheimer’s disease. Yet, advance studies are needed to characterize the active compound(s) and expose the possible mechanism of action.