The covalent attachment of polyethylene glycol (PEG) polymer chain to the therapeutic moieties is known as PEGylation, which prolongs the residence time of drug in to the body by preventing RES uptake and renal clearance because of increased molecular weight. PEG compounds used for PEGylation may require targetable functional group at one end for covalent modification. Previously it has been proved that PEGylation of liposomes results in improved pharmacokinetic and bio-distribution of therapeutic drugs. PEGylation of carbon nanotubes makes them water dispersible and long circulating moieties. The present study is the investigation of effect of PEGylation on liposomes and multi-walled carbon nanotubes (MWNTs) loaded with methotrexate (MTX) anticancer drug. MWNTs-MTX conjugate was prepared by non-covalent functionalization and liposome-MTX conjugate was prepared by thin film hydration technique. PEGylation of both conjugates was done by DSPE-mPEG 2000. The comparison study of drug loading, particle size and in-vitro drug release profile from both conjugates represents effective results from MWNTs than liposomes. Higher drug loading on to carbon nanotubes was achieved (2.26 mg on 1 mg MWNTs) than liposomes. Particle size of both conjugates was preferred for IV administration i.e below 200 nm. In-vitro drug release from MWNTs was faster as compared to liposomes at acidic environment (pH 5.8), which represents pH at cancer cells. So they can be targeted for cancer treatment. It can be conclude that PEGylation of carbon nanotubes for methotrexate gives better effect on cancer than the PEGylated liposomes.