The patients with end-stage of renal disease (ESRD) need to take oral phosphate binder. Traditional phosphate binders may leave the disadvantage of aluminum intoxication or cardiac calcification. Herein, Mg-Fe-Cl hydrotalcite-like nanoplatelet (HTln) is for the first time characterized as potential oral phosphate binder, with respect to its phosphorus uptake capacity in cow milk and cellular cytotoxicity. A novel method was developed for synthesizing the Mg-Fe-Cl HTln powder in different Mg2+: Fe3+ ratios where the optimization was 2.8:1. Addition of 0.5 g Mg-Fe-Cl HTln in cow milk could reduce its phosphorus content by 40% in 30 min and by 65% in 90 min. In low pH environment, the Mg-Fe-Cl HTln could exhibit relatively high performance for uptaking phosphorus. During a 90 min reaction of the HTln in milk, no phosphorus restoration occurred. In-vitro cytotoxicity assay of Mg-Fe-Cl HTln revealed no potential cellular cytotoxicity. The cells that were cultured in the HTln extract-containing media were even more viable than cells that were cultured in extract-free media (blank control). The Mg-Fe-Cl HTln extract led to hundred ppm of Mg ion and some ppm of Fe ion in the media, should be a positive effect on the good cell viability.