The binding properties and structural changes of mushroom tyrosinase enzyme, MT, due to its interactions with phenyl dithiocarbamate (I) and p-phenylene-bis dithiocarbamate (II), were investigated at 27 and 37°C in phosphate buffer (10 mmol·L −1 ) at pH = 6.8 by isothermal titration calorimetric (ITC). The extended solvation model was used to calculate the solvation parameters, which were attributed to the stability of this enzyme. Thermodynamic analysis indicated that the predominant mode of interaction was hydrophobic in the binding of compound I to MT, while the binding of II to MT essentially depends on electrostatic interactions. It seems that II is a more potent MT inhibitor due to its two charged head groups that are able to chelate copper ions in the active enzyme site. It was concluded that MT has two distinct sites for p-phenylene-bis and phenyl dithiocarbamate.