Abstract: Griseofulvin is a classic polyketide antifungal antibiotic, which has important application value in the fields of clinical treatment of skin fungal infection and agricultural biocontrol. Its industrial production depended on microbial fermentation, but the yield of wild strains was extremely low, which could not meet the market demand and industrial production requirements. The selection of high-yield griseofulvin strains was the premise of large-scale production. In this paper, the technological evolution of the selection of high-yield griseofulvin strains and fermentation optimization were systematically summarized, the research progress of its biosynthesis mechanism and multiple omics were expounded, and the application prospect of modern biotechnology such as gene editing in improving yield was further discussed, which provided guidance for the efficient production of griseofulvin.