The mixing enthalpies of N,N'-hexamethylenebisacetamide (HMBA) with glycine, l-alanine, and l-serine in d-mannitol solutions with different molar fractions have been determined by means of mixing-flow isothermal microcalorimetry at 298.15 K. The heterotactic enthalpic interaction coefficients (hxy, hxxy, and hxyy), in the molar fraction (x) range of d-mannitol from (0 to 0.0159), have been calculated in terms of McMillanMayer theory. The trends of hxy with the molar fractions of d-mannitol have been discussed based on the interactions between solute molecules under the participation of solvent molecules. The enthalpic contribution of the functional groups of solute molecules to hxy has been estimated according to the SavageWood additivity group (SWAG) approach. The influence of structural difference between glucose and d-mannitol on the hxy values of HMBA with glycine has been elucidated by combining the present results with our previous work.