In this study, the catalytic activity of calcined M3Al (M: Sr, Cd, Ni, Co, and Ca) and the effect of replacing divalent cations with Ca2+ in calcined MxCa3 - xAl hydrotalcite on the catalytic conversion of benzaldehyde and acetophenone to chalcone via Claisen-Schmidt condensation has been investigated. A series of M3Al and MxCa3 - xAl were synthesized by the co-precipitation method and characterized by SEM, BET, FT-IR, EDS, XRD, CO2-TPD techniques, and the Hammett indicator method. The results showed that the synthesized samples have normal surface area, high crystallinity, and three types of moderate, strong, and stronger basic sites. The catalytic activity is effectively dependent on the number of stronger alkaline sites. The effects of different parameters such as calcination temperature, solvents, catalyst amount, catalyst reusability, and the effects of electron-donating and electron-withdrawing groups were investigated. In optimum conditions over 0.04 wt% Sr0.5Ca2.5Al catalyst, at atmospheric pressure, 60 degrees C, in ethanol, yield (%) of chalcone was achieved at 87%.