By introducing Mg, Cu, Zn, Sn, and Mn into the synthesis processes of Ni and Al based hydrotalcite, Ni–Al layered hydrotalcite-derived catalysts with different metal compositions were prepared. In this paper, the effect of metal composition on the structure of Ni–Al layered hydrotalcite-derived catalysts is investigated, and then catalytic activities of prepared catalysts with different metal compositions on ethylene glycol aqueous-phase reforming are analyzed. The physicochemical properties of the Ni–Al layered hydrotalcite-derived catalysts were characterized by X-ray diffraction (XRD), temperature-programmed reduction (TPR), and nitrogen adsorption–desorption technology. The obtained hydrotalcite-derived catalysts were applied to the process of ethylene glycol aqueous-phase reforming (APR). The XRD results confirmed that the precursors of hydrotalcite-derived catalysts with metal compositions of Ni/Mg/Al, Ni/Cu/Al, Ni/Zn/Al, and Ni/Sn/Al had hydrotalcite crystalloid morphology. During the process of ethylene glycol aqueous phase reforming, all the catalysts showed high conversion of ethylene glycol (>90%), and the optimum hydrogen yield (73.5%) was obtained when using the catalyst with metal composition of Ni/Mg/Al at 225 °C under 2.6 MPa in nitrogen atmosphere for 2.5 h.