We report the preparation and characterization of a new organic-inorganic hybrid system composed of type-I collagen and ZnAl layered double hydroxide (LDH) particles loaded with β-hydroxy-β-methyl butyrate (HMB) by coprecipitation reaction. X-ray diffraction (peaks well agree with those reported in the literature), infrared spectroscopy (stretching bonds for both organic-inorganic compounds), and X-ray photoelectron spectroscopy confirmed the hybrid system retained HMB in the carboxylate form, and a small fraction turned to the acid form. In both cases, the HMB molecules are assembled to the LDH surface. The hybrid compound results in improved thermal stability for HMB and collagen, as shown by thermal analysis. Scanning electron microscopy data reflects different arrangements from LDH sheets with interesting physicochemical properties since LDH and collagen protect free HMB and make it more bioavailable and functional. In vitro studies as part of high-throughput screening strategies indicated that LDH hybrids reduced cell viability around 75-90%, which is an acceptable viability value because of the L6 cell line susceptibility. However, all new nanomaterials must be carefully analyzed by different toxicity tests because a single test does not evaluate complete physiological compartments.