Abstract— <p>In this research, the performance of polyethylene glycol (PEG) as a nanocarrier for the targeted drug delivery of cyclophosphamide (CLP) was investigated by density functional theory, infra-red, frontier molecular orbital and natural bonding orbital computations. The achieved results showed the interaction of CLP with PEG is experimentally feasible. The calculated thermodynamic parameters showed CLP adsorption process is spontaneous, exothermic and two sided. The impact of temperature and solvent on the interactions was also checked out and the results showed the presence of water as the solvent does not affect the interactions. Besides, by increasing of temperature CLP interactions with adsorbent become weaker indicating PEG can be employed as a temperature sensitive drug carrier. The increasing of dipole moment and also the decline of chemical hardness and bandgap showed when CLP adsorbs on the surface of PEG its chemical reactivity and bioavailibity improves substantially. The natural bonding orbital results demonstrated CLP interaction with PEG has a physisorption nature.</p>