The study explored the influence of plant extracts on neuronal degeneration caused by toxic β-amyloid in a transgenic APP/PS1 mouse model of Alzheimer‘s disease. Daily oral application of extracts of Hypericum perforatum and Sideritis spp. attenuated Aβ-induced histopathology and alleviated memory impairments in APP/PS1 mice. In detail, both extracts (i) decreased intracerebral Aβ42 and (ii) Aβ plaques, (iii) rescued neocortical neurons, and (iv) restored cognition to healthy control levels due to an enhanced Aβ42 export activity of ABCC1 and an increased phagocytic microglia activity.