Abstract: Ramelteon (RMT) is an agonist of the melatonin receptor, used for treatment of insomnia. Molecular modelling analyses based on molecular mechanics, semi-empirical (PM3) and DFT (at B3LYP/6-31G* level) calculations show that RMT and its metabolites RMTM1, RMTM2, RMTM3 and RMTM4 have moderately large to large LUMO-HOMO energy differences so that the compounds would be moderate to highly inert kinetically. In spite of its kinetic inertness, the metabolism of RMT takes place rapidly because of the involvement of enzymes. The molecular surfaces RMT and its metabolites are found to abound in neutral (green) and electron-rich (red and yellow) regions so that the compounds may be subject to both lyophilic and electrophilic attacks. The absence of any significant amounts of electron-deficient (blue) regions on the molecular surface means that the compounds may not react with cellular glutathione and nucleobases in DNA. This means that RMT and its metabolites may not induce cellular toxicity (associated with glutathione depletion) and may not also cause DNA damage (associated with oxidation of nucleobases in DNA). Rather, the compounds may act more like antioxidants.