AMPA and NMDA ionotropic glutamate receptors are the most prominent therapeutic targets in the broad spectrum of neurological diseases. Here we design novel peptide binders to these receptors, which are able to modulate these receptors’ physiological activity. We demonstrate that designed peptides have high affinity to selected targets in comparison to small molecules agonists by using molecular dynamics methods as well as modulator activity on rat cortical neuronal cell cultures by fluorescent calcium microscopy.