Starch, being a polymer of excessive demand for the development of products of pharmaceutical importance, has been tremendously treated in many ways for improving the desired characteristics such as viscosity, paste clarity, digestibility, swelling, syneresis, and so forth. In the present study, alkali-extracted starch of mandua grains (Eleusine coracana; family Poaceae) was treated with epichlorohydrin for cross-linking and the modified starch was assessed for swelling, solubility, water binding capacity, moisture content, and degree of cross-linking. The digestion resistibility of modified starch was analyzed in simulated gastric fluid (pH 1.2), simulated intestinal fluid (pH 6.8), and simulated colonic fluid (pH 7.4). The structural modifications in treated mandua starch were analyzed by Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (XRD), scanning electron microscopy, thermogravimetric analysis, and C13 nuclear magnetic resonance (13C NMR). The results of the study reflected the significant modification in mandua starch after treatment with epichlorohydrin (1.0% w/w sdb, solid dry basis). The degree of cross-linking of treated mandua starch was 85.15%, and the swelling capacity of mandua starch changed from 226.51 ± 2.175 to 103.14 ± 1.998% w/w after cross-linking with epichlorohydrin. A remarkable increment in digestion resistibility was observed in modified mandua starch. The XRD pattern and FTIR spectra revealed the presence of resistant starch after chemical modification. The decomposition pattern of modified mandua starch was also different from extracted mandua starch. All the results reflected the effective modification of mandua starch by epichlorohydrin and the formation of resistant starch to a significant content. The treated mandua starch may have the potential in developing various preparations of food, nutraceuticals, and pharmaceuticals.