Four Cu-Mg-Al mixed metal oxides (MMO) were synthesized through the calcination of layered double hydroxides (LDHs). These catalysts were fully characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), Brunauer-Emmett-Teller surface area (BET), and inductively coupled plasma optical emission spectrometer (ICP-OES). The catalytic efficiency of porous metal oxides derived from LDHs has been tested successfully for the synthesis of bis(indolyl)methanes via the Friedel–Crafts alkylation of indoles with aromatic aldehydes under solvent-free microwave irradiation. The Cu-Al MMO showed the best catalytic activity to produce the expected products up to 98% yield and 100% selectivity for only 20 min under solvent-free microwave irradiation. Moreover, the catalyst can be recovered quickly from the reaction mixture by filtration and reused several times without significant loss of the reactivity.