The lemon essential oil (LEO), extracted from the fruit of lemon, has been used to treat multiple pathological diseases, such as diabetes, inflammation, cardiovascular diseases, depression and hepatobiliary dysfunction. The study was designed to study the effects of LEO on cognitive dysfunction induced by Alzheimer’s disease (AD). We used APP/PS1 double transgene (APP/PS1) AD mice in the experiment; these mice exhibit significant deficits in synaptic density and hippocampal-dependent spatial related memory. The effects of LEO on learning and memory were examined using the Morris Water Maze (MWM) test, Novel object recognition test, and correlative indicators, including a neurotransmitter (acetylcholinesterase, AChE), a nerve growth factor (brain-derived neurotrophic factor, BDNF), a postsynaptic marker (PSD95), and presynaptic markers (synapsin-1, and synaptophysin), in APP/PS1 mice. Histopathology was performed to estimate the effects of LEO on AD mice. A significantly lowered brain AChE depression in APP/PS1 and wild-type C57BL/6L (WT) mice. PSD95/ Synaptophysin, the index of synaptic density, was noticeably improved in histopathologic changes. Hence, it can be summarized that memory-enhancing activity might be associated with a reduction in the AChE levels and is elevated by BDNF, PSD95, and synaptophysin through enhancing synaptic plasticity.