In this study, calcium oxide as a heterogeneous catalyst for biodiesel production was prepared by a simple calcination process at 800 degrees C for snails shells collected from Egyptian shorelines. D-optimal design of experiments and response surface methodology was applied to analyze the influence of four process variables; methanol:oil (M:O) molar ratio, catalyst concentration (wt%), reaction time (min), and mixing rate (rpm) on biodiesel production through transesterification of waste frying corn oil at 60 degrees C using the prepared biocatalyst. A second order quadratic model was obtained to predict the % biodiesel yield and it adequately described the studied experimental range. Based on the experimental analysis and response surface methodology study, the most suitable operational conditions for this process were: M:O, 6:1 molar ratio; catalyst concentration, 3 wt%; reaction time, 60 min; and mixing rate, 200 rpm. The corresponding predicted % yield of biodiesel was 96.76% and the experimental one was 96%. The activity of the produced green catalyst was comparable to that of chemical CaO and immobilized enzyme Novozym 435.