Inhibition of enzymes involved in the nonmevalonate pathway of isoprenoid biosynthesis represents a promising strategy for the development of novel antimalarial agents. A small series of reverse hydroxamate-based fosmidomycin analogues was synthesized and evaluated for their inhibitory activity against the recombinant 1-deoxy-D-xylulose 5-phosphate reductoisomerases (DXRs) of Escherichia coli and Plasmodium falciparum, as well as for their in vitro antiplasmodial activity and cytotoxicity.