Surfactants are substances applicable in the removal of heavy metals from contaminated soil. This study aims to investigate the effects of surfactant mixtures, composed of nonionic, anionic, and cationic surfactants, on the removal efficiency of Cd and Zn by mixture design (MD). Central composite rotatable design (CCRD) was integrated to optimize the conditions of contaminated soil washing. However, as representatives of each type of surfactant, a single surfactant with the most effective Cd removal was selected for each type before MD and CCRD studies. Sodium dodecyl sulfate (SDS) and sodium laureth sulfate (SLES) were the most effective anionic surfactants, while dodecyl trimethyl ammonium bromide (DTAB) and polysorbate 80 (Tween 80) were chosen to represent cationic surfactants and nonionic surfactants, respectively. Two systems of SDS-DTAB-Tween 80 and SLES-DTAB-Tween 80 were studied to examine their roles in Cd and Zn removal by MD. The results indicate insignificant enhancement in mixed surfactant systems for Cd and Zn removal. DTAB was identified as an ineffective surfactant, but at present, the presence of Tween 80 in both systems compensated for the use of SDS and SLES. The system containing SLES was selected to study CCRD because of its low cost and biodegradation. Cd and Zn removal efficiencies were 45.2% and 47.7%, respectively, at 40 mmol/L of 5-mL SLES solution per gram of soil with a 200-rpm shaker speed for 8 h. The Cd concentration of treated soil met Thailand’s agricultural soil standard. However, the further increase in removal efficiency should be considered.