The objective of this study was to evaluate the neuroprotective effect of quercetin with donepezil in scopolamine-induced amnesia in rats.Five groups of adult male Wistar rats (12 months old) weighing 180-200 g ( = 6) were used. The normal control group received normal saline and test group animals were pretreated orally with quercetin (25 mg/kg), donepezil (3 mg/kg), and a combination of quercetin (25 mg/kg) with donepezil (3 mg/kg), respectively, dosed at every 24 h interval for 14 consecutive days, afterward amnesia was induced by scopolamine (3 mg/kg) on the 14 day through intraperitoneal route. Cognitive performance was assessed by the Morris water maze, elevated plus maze, and passive avoidance paradigm. Acetylcholinesterase enzyme (AchE) level, biochemical markers such as lipid peroxidase (LPO), glutathione (GSH), β amyloidlevel, and histopathological study of rat brain were estimated. Statistical analysis was done by one-way analysis of variance, followed by Dunnett's test. ≥ 0.05 was considered statistically significant.Pretreatment with quercetin, donepezil, and their combination showed a significant increase in escape latency, step-through latency, and decreased transfer latency in respective cognitive models of the Morris water maze, passive avoidance test, and elevated plus maze. Further coadministration significantly decreased AchE level, β amyloidlevel as compared to individual therapy. Biochemical markers such as elevated GSH, decreased LPO were observed, and histopathological studies revealed the reversal of neuronal damage in the treatment group ( < 0.05) as compared to scopolamine-treated control group.Pretreatment with quercetin potentiates the action of donepezil in scopolamine-induced amnesia in rats. The improved cognitive memory could be due to the synergistic effect of the drugs by decreasing AchE level, β amyloidlevel, and antioxidant action in rat brain.