Aging is a complex and inexorable phenomenon, entailing several physiological changes. Impaired memory skills are associated with cell death in the hippocampus as a result of the age-related buildup of free radicals. D-galactose can artificially accelerate brain aging, causing memory impairment in mice due to neuroinflammation and oxidative stress. Numerous phytoconstituents found in Angelica keiskei possess anti-oxidant, anti-inflammatory, and memory-enhancing properties. In this study, we sought to determine the effects of an ethanol extract from the leaves of A. keiskei (EELAK) on spatial memory in mice with impaired memory functions due to D-gal. Here, we showed that administering 300 mg/kg BW/day of D-gal orally for a duration of 28 days significantly decreased spatial memory as quantified by the Morris Water Maze, and this was linked to a marked increase in hippocampal acetylcholinesterase (AChE), inflammation, and oxidative stress. The spatial memory of D-gal-induced mice was markedly enhanced by 20 mg/kg BW/day of EELAK, demonstrating its potent memory-boosting properties. The mice treated with EELAK also showed a notable decrease in hippocampal neuroinflammation (p65 NF-kB, NO, and TNF-α protein) and an increase in antioxidant activity (elevated SOD activity and reduced MDA levels), suggesting its potent neuroprotective activity. In conclusion, our results establish for the first time that by reducing oxidative stress and neuroinflammation, EELAK enhances spatial memory. Hence, for the prevention and treatment of age-related neurodegenerative illnesses like Alzheimer's disease, EELAK may be a useful therapeutic approach.