Solid base catalysts are highly demanded in many heterogeneous catalysis processes, but insights on active sites and structure–property correlation have rarely been revealed and remain a challenge. Herein, activated MxAl-layered double hydroxides (denoted as re-MxAl-LDH, M = Ca, Mg), as solid base catalysts toward the aldol condensation reaction, were prepared via a two-step procedure: calcination of the MxAl-LDH precursor to produce MxAl-mixed metal oxide (MxAl-MMO), followed by a further rehydration treatment. Structural characterizations confirm that re-CaxAl-LDH and re-MgxAl-LDH show similar morphology, particle size, specific surface area, and pore size distribution. However, a combination study including XPS, EXAFS, CDCl3–FTIR, and DFT calculations verifies that the host layer of re-CaxAl-LDH contains a distorted Ca(OH)6 octahedron with an additional Ca–OH coordination that provides weak Bronsted basic site; in contrast, re-MgxAl-LDH consists of a Mg(OH)6 octahedron structure accompanied by surface ...