The current clinical symptomatic therapy for Alzheimer's disease involves increasing acetylcholine levels in the brain by inhibiting acetylcholinesterase. However, the effectiveness of acetylcholinesterase inhibitors decreases as the disease progresses, leading to many side effects including over-inhibition of other enzymes and hepatic injury. Herein, we investigate the effects of the direct delivery of a low-dose of acetylcholine via human serum albumin nanoparticles to brain. This novel nanodrug improved both spatial learning and memory capability, whereas it reduced oxidative damage in mice. More importantly, damage to the liver or interference with the inherent neurotransmitter generation due to supplementation were almost absent. Our study is the first to demonstrate that supplementation of acetylcholine-loaded nanoparticles might offer a better therapeutic option in the ease of Alzheimer's disease.