The reactivity of few novel high‐spin Fe(II) complexes of Schiff base ligands derived from 2‐hydroxynaphthaldehyde and some variety of amino acids with the OH− ion has been examined in an aqueous mixture at the temperature range from 10 to 40°C. Based on the kinetic investigations, the rate law and a plausible mechanism were proposed and discussed. The general rate equation was suggested as follows: rate = kobs[complex], where kobs. = k1 + k2[OH−]. Base‐catalyzed hydrolysis kinetic measurements imply pseudo–first‐order doubly stage rates due the presence of mer‐ and fac‐isomers. The observed rate constants kobs are correlated with the effect of substituent R in the structure of the ligands. From the effect of temperature on the rate base hydrolysis reaction, various thermodynamic parameters were evaluated. The evaluated rate constants and activation parameters are in a good agreement with the stability constants of the investigated complexes. Moreover, the reactivity of the investigated complexes toward DNA was examined and found to be in a good agreement with the reported binding constants.