Layered double hydroxides (LDHs) in which magnesium was partially substituted by copper or iron in the hydrotalcite-like layer were synthesized by a coprecipitation method. The effects of the substitution on the physicochemical properties of the samples were studied by using various techniques such as X-ray diffraction (XRD), X-ray fluorescence (XRF), N-2 adsorption, scanning electron microscopy (SEM), thermogravimetry (TGA), X-ray photoelectron spectroscopy (XPS). After the thermal treatment the samples were tested as catalysts for the process of methylamines (MAs) synthesis from methanol and ammonia. The catalytic behaviors of the substituted samples are defined by a non-equilibrium distribution of MAs with monomethylamine (MMA) the favored product for the catalytic sample derived from CuLDH and dimethylamine (DMA) the main product for the catalyst derived from FeLDH. Reduction increases the selectivity to lower substituted amines: at 85% conversion of methanol the MMA contribution in the MAs distribution is 67% for the reduced catalytic sample containing copper whereas the DMA contribution is nearly 78% for the reduced catalytic sample containing iron. On the contrary when MgAlLDH is used as a catalyst precursor trimethylamine (TMA) has the main contribution in the characteristic MAs distribution. The nature of the substituted metal and the bifunctionality of the samples contribute in establishing the catalytic properties for the process of MAs synthesis from methanol and ammonia.