In Alzheimer’s disease (AD), acetylcholinergic (ACh) neurons are impaired at early pathological stage of AD, and amyloid β (Aβ) oligomers are thought to be a crucial molecule for triggering neurodegenerative processes in AD. In the present study, we first established an in vitro Aβ oligomer-induced neuronal cell death model using human induced pluripotent stem cell (iPSC)-derived ACh neurons and O-acyl isopeptide of Aβ, which reverts to natural form of Aβ under the neutral pH conditions. In the processes of neurodegeneration in this model, Aβ was tightly attached dendrites and mitochondrial dysfunction was induced. We next identified an Aβ-binding low molecular weight compound, plantainoside B, from the herbal extract of Bacopa monniera, which is used for memory enhancement in Ayurvedic medicine. Plantainoside B attenuated mitochondrial dysfunction and exert neuroprotection against Aβ neurotoxicity. Moreover, the ¹²⁵I-labeled plantainoside B showed a high affinity to brain sections obtained from a model mouse of Aβ plaque formation and Aβ oligomers in gel-loading experiments. Results indicate a possibility for the development of neurotheranostics approach for the strategy of AD treatment.