Abstract : The bio-functional molecule RES is present in grapes and mulberries. The current study aims to green synthesis of RES-CMCS nanoemulsion with low viscosity chitosan to test its protection of colon against carcinoma. The RES-CMCS produced was characterized using Zeta potential, particle size, morphology, and entrapment efficacy measurements. It was also examined for its colon protective activity against DMH induced colon carcinoma in mice model. The RES-CMCS had spherical shape with a mean particle size of 54.7 nm, a zeta potential of (-) 59.4 mV, and an entrapment efficacy of 85.46 %. Exposure of mice with RES-CMCS and 5-Fluorouracil, individually and/or in combination significantly normalized colon CAT, GSH, NO, SOD, COX-2, TNF-α, caspase 3 and CEA as well as SMAD-2, SMAD-3, TGF-β and TGFβR genes expression when compared to DMH administrated mice. The findings show that RES-CMCS could be employed as a novel pharmaceutical medicine strategy in the protection of colon against cancer by regulation of antioxidant enzymes as well as inflammatory mediator's gene expression.