Hydration parameter h values of the hydrophobic l-amino acids (l-alanine, l-valine, l-leucine, l-isoleucine, and glycine as a reference) were estimated in water using the viscosity B-coefficients and partial molar volumes, and the food macromolecular interactions were explored in aqueous solutions at 25 °C using the apparent viscosities of macromolecular solutions (polyethylene glycol 3500, dextran T40, guar gum, locust bean gum, apple pectin, citrus pectin, sodium alginate, and xanthan gum) with l-amino acids (l-alanine, l-valine, and glycine as a reference). An increased number of hydrophobic groups were associated with viscosity B-coefficient values, the partial molar volume values, and hydration of approximately 1.4 mol of water per carbon-equivalent. When hydrophobic l-amino acids were added to food macromolecular solutions, the relationship between the apparent viscosity and amino acid molality could be expressed using linear regression lines; the slopes of these lines may reflect macromolecular interactions. Using this novel parameter, the contributions of the hydrophobicity of amino acids to macromolecular interactions can be compared. Glycine decreased and l-valine increased the apparent viscosities of almost all polyelectrolytes (i.e., pectins and alginate) in water, but the effects on nonelectrolytes were less marked (guar gum with glycine is an exception). The effects of l-alanine varied. However, these amino acids did not change the viscosity of xanthan in water, although xanthan is a polyelectrolyte. Thus, the low sensitivity of macromolecular interactions of xanthan gum on the effect of these hydrophobic l-amino acids has been demonstrated to be favorable for use as a stable food thickener.