This goal of this study was to evaluate the effectiveness of a new coagulant extract from pumpkin seeds (PSC) for removing turbidity and organic compounds from different natural surface waters. Two design experiment methods, namely central composite design (CCD) and response surface methodology (RSM) were used to optimize PSC for removal of turbidity and organic matter via the chemical oxygen demand (COD) of surface water. The CCD results indicated that more than 74.7% of COD and 94.4% of nephelometric turbidity unit (NTUs) were removed under optimized conditions (pH = 7.4; mPSC = 1.5 g/L; time: 88 min). They allowed for final effluent with significantly higher quality in terms of organic content and safe to Vibrio fischeri to be obtained