Background: The goal of this study was to evaluate the cerebroprotective and cognition-enhancing activities of the aqueous Vitex trifolia ( Vt ) L. (Verbenaceae) leaf extract against scopolamine-induced amnesia and in normal rats. Methods: Reference or working memory and long-term memory in rodents were tested by experimental paradigms like passive avoidance (PA) and T-maze (TM), respectively. TM and Morris water maze (MWM) were used to screen putative spatial or localization task and the navigation memory-enhancing activities of Vt extract, respectively. In both the PA and TM models, scopolamine (0.5 mg/kg, intraperitoneal, 30 min prior to the trial) was used to induce amnesia, and donepezil (3 mg/kg/day for 15 days) was used as a standard antiamnesic drug. In MWM, two doses of Vt extract were tested against normal control rats. The aqueous Vt extract was prepared as a suspension in 0.5% carboxymethyl cellulose and administered orally at two doses (10 and 20 mg/kg/day) for 15 days to the respective group of rats. Results: The higher dose (20 mg/kg) of plant extract exhibited significant (p<0.01) antiamnesic activity in the PA and TM models vs. the control. In the MWM test, at probe trial, Vt extract 20 mg/kg showed the least escape latency time, which was statistically significant (p<0.01) and exhibited maximum percentage of time spent in the probe quadrant by 60.75%. Conclusions: These results partly substantiate the traditional use of Vt leaves for improvement of cognition, indicating that daily administration of Vt leaves differentially could modulate short- and long-term learning and memory in rats probably through its battery of anticholinesterase, procholinergic, anti-inflammatory, antioxidant, and neuroprotective activities.