The excessive and irrational use of organophosphate insecticides in our lives has resulted in a serious environmental problem, necessitating the proposal of novel and cost-effective plans to remove these organophosphate insecticides from agricultural or industrial wastewater. In this approach, we investigated the use of phyllosilicate clay as a low-cost and environmentally friendly adsorbent to eliminate an organophosphate insecticide (Diazinon DZN) from an aqueous medium. To achieve an adequate elimination of this insecticide from contaminated water, three main parameters including clay dose ( D c ) (0.1–1.5 g L−1), medium pH (5–9), and initial DZN concentrations ( C DZN ) (55–40 mg L−1) were optimized using a multivariable optimization based on Box-Behnken Design (BBD). The response surface method (RSM) and composite desirability function technique were used to find the ideal conditions for the three input variables and the adsorption amount ( Q e ) was selected as the output variable. The higher adsorption amount ( Q max ) was achieved with an adsorbent amount of 1.5 g L−1 in an acidic medium (pH = 5) at room temperature and a Diazinon initial dose of 25.85 mg L−1, with a maximum adsorbent loading of 12.20 mg g−1. The nonlinear modeling study showed that the adsorption kinetics of Diazinon follows the pseudo-second-order model. The thermodynamic study shows that the DZN removal process is exothermic, spontaneous, and of a stable configuration.