In this paper, the sequestering ability of amoxicillin and ampicillin toward Mg2+ in NaCl aqueous solutions at different ionic strengths I = (0 to 1.0) mol.kg(1) and temperatures of T = (288.15 to 318.15) K was investigated by potentiometry (ISE-H+, glass electrode). The complex formation constants determined at different ionic strengths and temperatures were modeled by means of the DebyeHuckel equation and the Specific ion Interaction Theory (SIT). From the results, a weak ability of the two penicillins to bind the metal ion can be observed; in fact, the stability constants of the ML species (M = Mg2+ and L = amoxicillin or ampicillin) are log beta = 4.348 and 3.242 at infinite dilution and T = 298.15 K, respectively. The dependence of the formation constants on the temperature was modeled by means of a vant Hoff equation, which allowed us to calculate the enthalpy and entropy change values of formation of each species. The sequestering ability of amoxicillin and ampicillin toward Mg2+ in the different experimental conditions (pH, ionic strength, temperature) was quantified by means of a sigmoid equation and of the pL(0.5) parameter. The pL(0.5) values reflect the low stability constant values of the species; as an example at I = 0.15 mol.kg(1), pH = 7.4, and T = 298.15 K, we have pL(0.5) = 2.52 and 2.78, for Mg2+/amox(2-) and Mg2+/amp(-) systems, respectively.