The use of nano calcium oxide as a catalyst in biodiesel production has gained attention due to its high catalytic activity, low cost, and environmental friendliness. It efficiently converts triglycerides to fatty acids and methyl esters. In the present study, nano CaO was prepared by precipitation and characterized by various techniques. The results showed that the nano CaO has high purity, nanoscale crystal size, good thermal stability, and high specific surface area. Biodiesel was produced by transesterification from waste cooking oil, methanol, and the nano catalyst. Response surface methodology was applied to predict the optimum parameters for the production of the biodiesel based on its yield. The produced biodiesel was characterized by FTIR spectroscopy and GC‐MS and evaluated according to ASTM D6571.