Hydrotalcites and amino acid functionalized hydrotalcites (aa-HTs) were synthesized using the co-precipitation method. These compounds were characterized using X-ray diffraction (XRD), inductively coupled plasma-optical emission spectroscopy (ICP-OES), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). The optimal siRNA binding capacity was determined using gel retardation assays. Cytotoxicity studies using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the siRNA:HT complexes were relatively non-cytotoxic to HeLa-tat-luc cells. Gene silencing studies showed that the aa-HTs elicited significantly higher levels of gene knockdown when compared to the non-functionalized HTs. Overall, these HTs have shown the potential to bind, protect and efficiently deliver siRNA, in vitro.