In this study, the coagulation‐flocculation of a wastewater discharged from a marble processing plant was statistically analyzed and optimized. To make a systematic investigation on the coagulation‐flocculation of the highly turbid wastewater (>1000 NTU), the response surface methodology was used to estimate a capable quadratic model with R‐squared value of 98.84%. According to this model, the most critical parameter was the suspension pH with a p‐value < 0.0001. Furthermore, the PEO‐flocculant was proven as a substantial agglomerating reagent specifically at pH 12. On the other hand, no significant turbidity removal was observed upon the addition of the Fe‐coagulant. When the experimental parameters of the coagulation‐flocculation were optimized, it was found out that the minimum supernatant turbidity value of 3.81 NTU can be achieved by using the minimum amount of the Fe‐coagulant:50 mg/l, and the maximum amount of the PEO‐flocculant of 1.5 ppm at pH 11.5‐12.0. In conclusion, it was proved that the significance of the calcium dissolved from the marble particles was greater than the Fe‐coagulant in this process. The hydrolyzed calcium (CaOH+) species established a chemical bridge between the particle and the polymer and, as a result, enhanced the performance of the flocculation at the alkaline pH values.