This work is aimed at the development of a semi-continuous mechanochemical process for biodiesel production and the subsequent valorization of glycerol, its by-product, via its conversion into calcium diglyceroxide using the same mechanochemical reactor. This basic solid catalyzes the methanolysis of vegetable oils. The implementation of a semi-continuous process allows both the preparation of the solid catalyst and the methanolysis process, overcoming the miscibility problems of methanol and oil. Thus, a biodiesel yield higher than 90% is reached using a methanol:oil molar ratio close to stoichiometric value and 1.5 wt.% catalyst, after passing through the reactor with a flow rate between 4 to 45 L/h. This new process for biodiesel production can easily be scaled up and applied to the conversion of used cooking oils, without any significant yield decrease. A cost study was also performed, demonstrating that this is more economical than the conventional batch stirring-based process.