Colon-targeting drug delivery systems (CDDSs) are employed to improve the bioavailability of protein and peptide drugs through the oral route. So it is important to prepare the drug carriers for oral CDDS. In this study, the Enzyme-Resistant starch (RS) was studied for use as a vehicle in oral colon-targeting drug delivery. The characteristics of RS powders were investigated by X-ray diffraction, polarizing microscopy, DSC and SEM, and their film were examined by enzymatic digestion test. The results showed that RS could be a promising film-former for pharmaceutical coatings, having good stability to enzymatic digestion. Furthermore, a novel peroral formulation using RS coating and bovine serum albumin as a model drug was studied for colon-specific drug delivery in vitro. Drug release studies have shown that RS coating could delivery the drug to the colon and the release rate in simulated colonic fluids was dependent on the biodegradation of RS and its coatings. It is indicated that the RS coated tablet is a potential system for oral CDDS.