Proteins and small molecules in biological systems exhibit vibrational frequencies within the terahertz (THz) spectrum (0.3–100 THz), comparable with the energies of weak molecular interactions like hydrogen bonds and π-π stacking. This suggests that THz radiation could potentially modulate biological functions through resonance, while the mechanisms and effective frequencies for such regulation remain unclear. Using rhodopsin as a model, we investigated the effects of THz waves on the binding affinity between retinal and opsin in both its dark-inactive and light-activated states. We identified key residues and interactions for retinal binding to opsin and compared the conformational stability of retinal in the opsin pocket. By introducing THz waves of varying frequencies, we found that low-frequency waves modulate rotatable molecular conformations, while high-frequency waves regulate key chemical bond-mediated interactions. These findings reveal the potential of THz technology to selectively influence molecular interactions in biological systems, offering a new approach to control biological functions at the molecular level.