The uptake mechanism of heavy metal ions in Layered double hydroxides (LDHs) is investigated in this paper via solid-solution exchange experiments and first principle study. The structures of heavy metal doped LDHs are revealed with XRD, TEM and solid state NMR analysis combined with first principle calculations. The experimental results show that Cu2+ or Cr3+ ions are immobilized in the form of isomorphic substitution during reconstruction of calcined LDHs, forming a non-stoichiometric structure. The Cu2+ or Cr3+ ions are immobilized via isomorphic substitution for Mg2+ and Al3+ in the plate of the layered structure, respectively. The structure of Cu2+ doped LDHs is identified as as [Mg2+ (1-x)(1- z)Cu2+ (1-x)zAl3+ x(OH)2] Anx/ n·yH2O, where z is the Cu2+/Mg2+ molar ratio. The structure of Cr3+ doped LDHs is identified as [Mg2+ 1-x Cr3+ xzAl3+ x(1-z)(OH)2] An- (x+z)/n·yH2O, where z is the Cr3+/Al3+ molar ratio. The Cu2+ or Cr3+ ions from mixing water can be efficiently immobilized with Mg-Al LDHs in cement.