Layered double hydroxides (LDHs) are important components in terrestrial and extra-terrestrial environments. The presence of iron in these minerals provides them a wide potential application in environmental and materials sciences. In this work, the role of Fe in the crystallographic properties of LDHs M2+:M3+ 2:1 with Mg:(Fe,Al), Mg:Fe, Zn:(Fe,Al), and Zn:Fe is investigated by means of quantum mechanical calculations based on the density functional theory (DFT). Several relative proportions of Fe are studied. The cation ordering of these LDHs has been explored, finding useful insights for experimental synthetic paths of these minerals. The a and b cell parameters increase with the iron concentration. Some diffraction lines at high angle decrease in angle and increase in intensity with the increasing iron concentration. All of them agree with the experimental results. The iron substitutions tend to aggregate.