The current study investigated the neuroprotective effects of rutin hydrate (RH) in an Alzheimer’s disease (AD)-like learning and memory impairments rat model. Since AD is an age-related degenerative brain disorder characterized by a progressive worsening in cognitive function and memory, RH may be a potential drug for the treatment of AD-like memory loss, and this work is aimed to evaluate whether RH has neuroprotective effects in memory deficits induced by scopolamine (SCO). In our study, RH demonstrated beneficial effects as a neuroprotector in the brain and improved learning, memory, and synaptic plasticity in a rat. Rats were administered RH (100 mg/kg) and SCO (1.5mg/kg), and performed behavioral tests such as Morris water navigation test, Y-maze test, and passive avoidance test to evaluate the ability of learning and memory. In accordance with these findings, RH behaviorally attenuated SCO-induced shortening of step-through latency in the PA test, increased the percent of alternation in the Y-maze, and increased the time spent in the target zone in the MWN. Moreover, the neuroprotective effect of RH on learning and memory was investigated through the long-term potential on organotypic hippocampal slice cultures. RH increased the total activity of field excitatory postsynaptic potential (fEPSP) following theta burst stimulation and attenuated SCO-induced blockade of fEPSP. This approach could potentially be used as a therapeutic strategy for the restoration of learning and memory function and the prevention of the progression of AD. SCO treatment decreased the levels of BDNF/TrkB/ERK/CREB/Bcl2 and increased the Bax protein level in rat hippocampus. RH ameliorated the expression of these proteins by attenuating SCO-induced up or downregulation in the hippocampus. Based on these findings, the results highlight the molecular and cellular mechanisms through which RH is proposed to exert its neuroprotective effects in the prevention and treatment of learning and memory deficit disorders.