In exploring the application of natural coagulants in industrial wastewater treatment, plant-based coagulants have been gaining more interests due to their potential such as biodegradability and easy availability. Hylocereus undatus foliage as a plant-based coagulant has been proven to be efficient during the coagulation-flocculation process; however, limited research has been reported focusing only on palm oil mill effluent (POME) and latex concentrate wastewater. In addition, no previous study has been carried out to determine the performance evaluation of Hylocereus undatus foliage in treating different types of wastewater incorporating different operating conditions using optimization techniques. Hence, this study employed response surface methodology (RSM) in an attempt to determine the performance evaluation of the coagulant in paint wastewater treatment. Four independent factors such as the pH value, coagulant dosage, rapid mixing speed and temperature were chosen as the operating conditions. Three water parameters such as turbidity, chemical oxygen demand (COD) and suspended solids (SS) were chosen as responses in this study. Results revealed that through central composite design (CCD) via Design Expert software, the optimum conditions were achieved at pH 5, coagulant dosage of 300 mg/L, rapid mixing speed of 120 rpm and temperature at 30 °C. The experimental data was observed to be close to the model predictions with the optimum turbidity, COD and SS removal efficiencies found to be at 62.81%, 59.57% and 57.23%, respectively.