The invention relates to the field of organic synthesis and pharmaceutical chemistry and particularly relates to a Cleistanone derivative, a preparation method thereof and an application thereof in the preparation of antibacterial drugs. According to the invention, a novel Cleistanone derivative is synthesized, and a preparation method of the novel Cleistanone derivative is disclosed. Shown by pharmacological experiments, the Cleistanone derivative disclosed by the invention has an antibacterial effect and has a value in the development of the antibacterial drugs.