In this work, Al cation was gradually replaced by FeIII in the composition of Layered Double Hydroxides (LDH) and systematically investigated for LDH application as drug carriers, ultimate aiming to improve their biointegration. The incorporation of FeIII into LDH layers, as well the intercalation of organic anions in the iron-based materials, is challenging. Several studies approach the intercalation of non-steroidal anti-inflammatory drugs such as anionic naproxen (NAP) into Al-LDH. Thus, NAP was applied here as a model drug for the study of compositional and structural aspects of novel FeIII-LDH carriers envisaging to shed light on the intercalation of other carboxylate drugs into these materials. LDH of general [M2FeyAl(1-y)(OH)6]An− compositions (MII=Mg or Zn; An−=anion of charge n) were investigated using two synthetic methods for NAP intercalation. Full X-ray diffraction profile refinement and a crystal-geometrical reasoning were used to strengthen the results interpretation. Unlike coprecipitation, in which probably NAP complexation with FeIII hinders LDH-NAP self-assembling, topotactic ion exchange demonstrated to be a potential approach.