Various layered double hydroxides (LDHs) were prepared by the co-precipitation method using the most common divalent and trivalent metal precursors. The resulting LDHs were studied for their performance in removing phosphate from aqueous test solution. The results have clearly demonstrated the influence of Ca and Mg as pre-cursor metals in synthesizing LDH compounds for removing phosphate. For the same LDH’s dose, more phosphorus was removed by Ca-based LDHs than Mg-based LDHs. Real effluent from a wastewater treatment plant with high phosphate concentration (3.4–10.4 mg-P/L) can also be treated with >90% removal by both Ca- and Mg-based LDHs depending on the selection of suitable dose. For Ca-based LDHs, the main removal process was observed to be as calcium-phosphate precipitation. Due to the loss of layered structure after first sorption/precipitation operation, Ca–(Fe or Al)-LDHs cannot be regenerated for reuse. However, Mg-based LDHs showed potentially applicable for the regeneration and reuse due to their stable nature in aqueous phase than Ca-based LDHs. On the other hand, when choosing CaMg-based LDHs for the phosphorus removal, the nature of Ca dissolution from such LDHs needs to be taken into account although they were demonstrated to be reusable with the efficiency of phosphate removal up to 64% at the fourth cycle.