The application of Response surface methodology (RSM) to design optimization is aimed at reducing the cost of expensive analysis methods (e.g. finite element method or CFD analysis) and their associated numerical noise. This research work is based optimization Of bio-fertilizer production from watermelon peels, in which Central Composite Design (CCD) under the Response Surface Methodology (RSM) was used to optimize the retention days and water ratio, (factors), while Nitrogen(N), Phosphorous (P) and potassium (K) were the responses.