To provide the underlying mechanism of the inhibiting effect of trehalose on the urea denatured protein, we perform classical molecular dynamics simulations of N-methylacetamide (NMA) in aqueous urea and/or trehalose solution. The site site radial distribution 'functions and hydrogen bond properties indicate in binary urea solution the replacement of NMA water hydrogen bonds by NMA urea : hydrogen bonds. On the other hand, in ternary urea and trehalose solution, trehalose does not replace the NMA-urea hydrogen bonds significantly; rather, it forms hydrogen bonds with the NMA molecule: The calculation of a preferential interaction parameter shows that, at the NMA surface, trehalose molecules are preferred and the preference Pot urea decreases slightly in ternary solution with respect to the binary solution: The exclusion of urea molecules in the ternary urea NMA trehalose system causes alleviation in van der Waals interaction energy between urea and NMA molecules. Our findings also reveal the following: (a)trehalose and urea induced second shell collapse of Water structure, (b) a reduction in the mean trehalose cluster size in ternary, solution, and (c) slowing down of translational motion of solution species in the presence of osmolytes Implications of these results for the molecular explanations of the counteracting mechanism of trehalose on urea induced protein denaturation-are discussed.