In this study, we have established an effective and novel nanocarrier system for the effective treatment of glioma. We have established the glioma tissue penetrating nanocarrier system by conjugating Pep-1 as a targeting ligand on the liposome surface to enhance the anticancer efficacy of cilengitide (CGL). The particles were nanosized and exhibited a controlled release of drug in both the pH conditions. The cellular uptake assay showed that conjugation of Pep-1 on the liposome surface remarkably increased the cellular uptake. The uptake of CGT-loaded Pep-1 peptide-conjugated liposome (PeCNL) increased to 89.8% compared to 47.5% for CNL indicating the efficient internalization of the nanocarriers. Consistently, PeCNL exhibited a significantly higher cytotoxic effect in cancer cells compared to that of non-targeted CGT-loaded liposome (CNL). PeCNL exhibited a higher apoptosis of cancer cells (∼35%) compared to that of CNL. Most importantly, PeCNL exhibited a significantly superior anticancer effect with tumor volume as low as ∼350 mm³ indicating the superior anticancer potential of targeted formulations. Similarly, PeCNL showed the lowest staining for Ki67 indicating that the targeted NP has the maximum effect in controlling the proliferation of cancer cells. Taken together, Pep-1 conjugated liposome could exhibit better antitumor efficacy when applied to IL-13R2 receptor overexpressed specific brain glioma.