This study investigated the optimization of a bio-coagulation process for surface water treatment using Moringa oleifera leaf extract as an eco-friendly natural coagulant. Response Surface Methodology (RSM) was implemented through a face-centered Central Composite Design (CCD), involving three operating factors: coagulant dose (0.5–2.0 g/L), coagulation speed (200–300 rpm), and coagulation time (2–3 min). Process performance was assessed through turbidity removal (%), color reduction (%), and final pH of water. Experimental results showed turbidity removal between 60.41 and 72.39%, color reduction between 16.53 and 38.58%, and final pH between 3.83 and 4.13. Analysis of variance confirmed the reliability of the developed models, with non-significant lack of fit for all responses. Turbidity removal was adequately described by a significant linear model (F = 37.44, p < 0.0001, R² = 0.8822), where coagulant dose, coagulation speed, and coagulation time were significant influencing factors, with coagulation time showing the strongest effect. This removal efficiency can be considered reasonable considering the very short coagulation time, the absence of conventional chemical coagulants, and the use of a crude plant-based extract. Color reduction was also fitted by a significant linear model (F = 70.71, p < 0.0001, R² = 0.9340), mainly controlled by coagulant dose and coagulation time, while coagulation speed was not significant. Final pH was best represented by a quadratic model (F = 25.68, p < 0.0001, R² = 0.9625), with coagulant dose and its quadratic effect as dominant terms. The optimized conditions were 1.046 g/L coagulant dose, 300 rpm, and 3 min, predicting 64.61% turbidity removal, 27.98% color reduction, and pH 3.98. The results demonstrate the potential of Moringa oleifera leaf extract for sustainable surface water clarification, although pH correction remains necessary for practical application.