N-Methyl-D-aspartate receptors (NMDAR) are essential for synaptic plasticity and cognitive function, making their modulation a promising strategy for treating disorders like schizophrenia and cognitive impairment. However, methods to selectively modulate NMDAR activity in the lesion's nucleus of the central nervous system remain limited. In this study, using whole-cell patch-clamp recordings, we demonstrated that frequency-specific (42.5 THz) terahertz irradiation significantly enhanced both the frequency and amplitude of NMDAR-mediated miniature excitatory postsynaptic currents (mEPSCs), a response closely linked to Ca²⁺ currents. The mechanism is elucidated via molecular dynamics (MD) simulations, revealing that 42.5 THz irradiation effectively alters the free energy landscape of Ca²⁺ permeating through the NMDAR channel. Specifically, THz photons resonated with key carboxyl groups at the Ca²⁺ binding site, leading to an increase in Ca²⁺ permeability and consequently enhanced mEPSCs. These findings suggest a novel physical therapy approach for treating cognitive deficits and neurological disorders associated with impaired NMDAR function.