The invention relates to the technical field of enzyme inhibitors, and especially relates to a hydroxamic acid derivative, and a preparation method and an application thereof. A hydroxamic acid groupin the hydroxamic acid derivative is chelated with active zinc ions in the active region of an LpxC enzyme, and contains a hydrophobic side chain combined with a hydrophobic channel in the LpxC enzyme, so good bactericidal activity and low toxicity of the hydroxamic acid derivative to the LpxC are ensured. The invention further provides the preparation method of the hydroxamic acid derivative. Thepreparation method has a short reaction time and a high yield.