Abstract: UDP-2, 3-diacylglucosamine pyrophosphate hydrolase (LpxH) is a key enzyme in the lipid A biosynthesis pathway of Gram-negative bacteria. Lipid A is an indispensable component of lipopolysaccharide (LPS), and LPS plays an important biological function in Gram-negative bacteria. Therefore, LpxH is considered one of the important targets in the research of antibacterial drugs. Based on the function and structure of LpxH enzyme, this review systematically summarizes and analyzes the currently reported LpxH inhibitors, and offers perspectives on future research directions. This review will provide ideas for the design of LpxH inhibitors and contribute to the development of new antibacterial drugs targeting LpxH.