Abstract: Griseofulvin is a classic polyketide antifungal antibiotic with significant application value in clinical treatment of skin fungal infections and agricultural biocontrol. Its industrial production relies on microbial fermentation, but the yield of wild strains is extremely low, unable to meet market demands and industrial production requirements. The selection of high-yield griseofulvin strains is the prerequisite for large-scale production. This article systematically summarizes the technological evolution of the selection of high-yield griseofulvin strains and fermentation optimization; elaborates in detail on the composition of its biosynthetic gene cluster and the functions of key enzymes as well as the core biosynthetic pathway, and introduces the related progress of discovered regulatory factors for griseofulvin biosynthesis; outlines the latest progress of multi-omics technologies in the research of Griseofulvin Penicillium. It also discusses the application prospects of modern biotechnologies such as gene editing in increasing yield and the development direction of metabolic engineering strategies, providing theoretical guidance and technical support for the efficient production of griseofulvin.