A series of hydrotalcite-like layered double hydroxides (LDHx) with different Mg/Al atomic ratios (x = 2–6) were prepared by using the co-precipitation method. Further calcination yields mixed oxides with tunable basicity. The basicity of the calcined LDHx (LDOx) strongly depends on the Mg/Al ratio and the calcination temperature. The resulting LDOx materials were used as solid base catalysts and evaluated in the transesterification between glycerol and dimethyl carbonate without use of organic solvent. The correlation between the basic properties of the solid catalysts and the catalytic performance was investigated. The activity of the LDOx catalysts was demonstrated to be proportional to the surface density of basic sites. LDO2 calcined at 600 °C exhibited maximum activity for the transesterification reaction. The beneficial effect of the optimum ratio of Mg/Al = 2 is related to its high total basicity. The LDO2 catalyst can be readily recycled while maintaining high catalytic activity and selectivity of glycerol carbonate.