Ginsenosides have been reported to improve memory impairments. However, the effects of metabolized minor ginsenosides on neuronal damage and cognitive function remain unclear. We investigated the effects of SGB121, ginsenoside F1 enriched ginseng extract, on scopolamine-induced cytotoxicity and cognitive deficits in vitro and in vivo, respectively. We observed that SGB121 reversed the scopolamine-induced apoptosis; mitochondrial membrane potential reduction; and dephosphorylation of Akt, glycogen synthase kinase-3beta (GSK313), and extracellular signal-regulated kinases (ERK) in SH-SY5Y cells. Oral SGB121 administration in ICR-mice oncedaily for 7 days significantly recovered scopolamine-induced memory impairment analyzed using Y-maze test and passive avoidance task. In mouse hippocampi, SGB121 restored scopolamine-induced decrease in ERK and cAMP response element-binding protein (CREB) phosphorylation and brain-derived neurotrophic factor (BDNF) expression. Furthermore, SGB121 decreased acetylcholinesterase expression both in SH-SY5Y cells and in mouse hippocampi. SGB121 demonstrated protective effects against neurotoxicity and memory impairments, suggesting its potential as oral therapeutics in neurodegenerative diseases.