Urea is a common osmolyte that unfolds proteins in aqueous urea solution. On the other hand, TMAO is a protecting osmolyte means it stabilizes the folded form of protein. Interestingly, TMAO prevents the denaturing ability of urea and helps a protein to stay in its folded form in aqueous urea-TMAO solution. Several theoretical and experimental studies have addressed on the destabilizing effect of urea, the stabilizing effect of TMAO and the role of TMAO to counteract the denaturing ability of urea. It has been shown that the preferential interaction of urea with the protein side-chains as well as protein backbone leads to an accumulation of urea around protein's solvation shell and eventually causes the protein unfolding. However, the complete molecular level understanding about the role of TMAO in stabilizing protein native folded structure either in aqueous TMAO solution or in water-urea-TMAO mixture is not established yet. Various contradictory theories are proposed to explain the role of TMAO in stabilizing protein native folded structure. The role of hydrophobic effect in protein folding is undeniable. Hence the study of the solvation of small hydrophobic molecules or association behaviors of hydrophobic molecules in osmolyte solutions is very important on this regard. Several simulations work concluded a favourable dispersion interaction between urea and hydrophobic moieties is responsible for a higher population of unfolded conformations of hydrophobic polymers or less positive solvation free energies of hydrophobic molecules in urea-water relative to neat water. It was also found using model hydrophobic solutes (except methane) that the Hydrophobic solvation is more favourable in ureawater mixture as the dispersion energy contribution is more favourable in aqueous urea solution in comparison to that in pure water. For the same reason, association of large hydrophobic molecules is reduced to certain extend in urea-water compared to that in pure water. Contrarily, the hydrophobic association in water-TMAO solution or in water-urea-TMAO is not well understood and several contradictory opinions are present in literature. The work of Athawale et al. had found that TMAO does not affect the strength of the hydrophobic interactions. Simulations studies also found a greater number of TMAO molecules preferentially bind to the folded form of hydrophobic chain than that of the unfolded form and that leads to a higher population of folded form in TMAO solution. Nair and van der Vegt showed by detailed thermodynamic analysis that TMAO stabilizes the collapsed hydrophobic polymer structures at low TMAO concentrations and the unfolded structures are stabilized at higher concentrations. Recent simulation studies from Ganguly et al. have shown that hydrophobic association is very sensitive to the choice of the force fields of TMAO molecule. It was found by Tah and Mondal that the collapsed form of a hydrophobic polymer is destabilized in mixed urea-TMAO solution.