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.