Vegetable tannery wastewater, highly laden with recalcitrant organics, is not easily treatable through biological processes. This study focuses on the use of response surface methodology in optimizing a coagulation-flocculation process for pretreatment of vegetable tannery wastewater. This study also assessed the possibility of replacing chemical coagulants such as aluminum sulphate with green alternatives such as cassava starch and orange peel powder. The effects of coagulant dosage and pH on three key wastewater quality parameters (chemical oxygen demand (COD) and total suspended solids (TSS)’s removal efficiencies as well as sludge volume index (SVI)) were also assessed. Quadratic models developed for all the three responses were adequate. The optimal conditions were attained at a pH of 3.17 and a dosage of 2.76 g/L for cassava starch coagulant, pH of 3.74 and a dosage of 5.16 g/L for orange peel powder coagulant, and pH of 6.09 and a dosage of 11.60 g/L for aluminum sulphate. The COD and TSS removal efficiencies as well as SVI achieved under these optimal conditions were 37.25%, 73.95%, and 14.80 mL/g, respectively, for cassava starch coagulant; 17.97%, 66.08%, and 19.87 mL/g, respectively, for orange peel powder coagulant; and 38.51%, 76.06%, and 29.57 mL/g, respectively, for aluminum sulphate. The outperformance of cassava starch over orange peel powder and its comparable results with aluminum sulphate makes the former a more environment-friendly alternative to aluminum sulphate for treatment of tannery wastewater.