The aim of the study was to develop a drug delivery system for specific targeting in colon cancer. We have developed Eudragit S-100 (ES) coated folic acid (FA) conjugated gliadin (Gd) delivery system for the effective targeting to the over expressed folate receptors (FRs) in colon cancer. The FA conjugate with Gd (FA-Gd) was synthesized and characterized by FTIR and 1H NMR, this developed conjugated was used to prepare curcumin (CU) loaded nanoparticles (NP) by desolvation method. FA-CU-GdNP was further coated with ES and ES-FA-CU-GdNP was obtained. The ES-FA-CU-GdNP were also capable of inducing cell caspase dependent apoptosis in Caco-2 cell lines and exhibit DNA intercalating activity. In therapeutic experiments the ES-FA-CU-GdNP was administered orally to HCT-116 tumor bearing nude mice. In vivo data of bio-distribution showed that ES-FA-CU-GdNP delivered maximum amount of NP in the colon and tumor, respectively after 12 hours, reflecting its targeting potential to the colon and tumor. Gamma scinti