Herbal medicines and supplements exhibit the phenomenon of neurohormesis, mechanisms that may prevent or mitigate neurodegenerative pathogenesis. Gephyrin’s role in the stabilization of receptors for inhibitory transmitters and regulation in postsynaptic activity makes it an important target for research and possible therapeutic approaches. The impairment of gephyrin function will also lead to cognitive impairment, which is a key symptom of Alzheimer’s disease. Phosphorylation of gephyrin by glycogen synthase kinase -3β is important for neuronal synaptic plasticity in modulating GABAergic transmission. This work aims to evaluate the potential of the interaction of artemisinins, curcumin, and flavonoids with the scaffolding protein gephyrin, the kinase GSK-3β, using molecular modeling methods. All studied compounds interact with targets with high affinity. Amino acid residues Asp327, Phe330, which are important for the interaction of gephyrin and artemisinins, are identical to those that mediate the interaction of gephyrin and the inhibitory mediator receptors. Therefore, modulation of interaction with receptors may be a promising strategy for drug development and pharmacological therapy of AD. Many of the amino acid residues of gephyrin that mediate interactions with receptors are located in the C-terminal E domain. Docking of all compounds revealed interaction in the ATP-binding site of GSK-3β with high affinity. Of all ligands, only DDHA displays a hydrophobic contact with Phe93 in the substrate-binding site, which is typical for inhibitors of peptide nature. Thus, the studied bioactive compounds exhibit multitarget neuroprotective action, cross the BBB, and may be considered as potential candidates for the treatment and prevention of AD.