We report that curcumin spray powder (CM-SD) alleviated scopolamine-induced memory impairment by suppressing scopolamine-induced ACh levels and upregulating hippocampal ChAT and memory susceptibility genes, including, BDNF, PI3K, Akt, ERK1/2, CREB, and CaMK IV in C57BL/6 mice. Previous studies have reported that scopolamine treatment in C57BL/6 mice significantly decreased step-through latency in the passive avoidance task test, hippocampus ACh contents, ChAT mRNA expression, and the expressions of memory susceptibility genes. In the present study, scopolamine treatment increased escape latency times in the Morris water maze test, the activity of hippocampal AChE in C57BL/6 mice, and disrupted the cerebral cortex anti-oxidant defense system. However, CM-SD, treatment dose-dependently reduced these effects in our scopolamine-induced C57BL/6 mouse model of amnesia. Our findings indicate CM-SD is a potential medicinal food ingredient that might ameliorate various types of memory impairment.