Abstract: Natural products derived from microorganisms are one of the important sources of drug lead compounds. In recent years, the research of microbial co-culture to produce various natural products has developed rapidly. Microbial co-culture is an effective method to induce microbial production of novel secondary metabolites by simulating habitats that may activate gene clusters for cryptic secondary metabolite biosynthesis. Compared with the single strain fermentation, co-culture increased the chemical diversity of secondary metabolites and improved the biological activity or yield of secondary metabolites. This paper reviewed the recent results of microbial co-culture research from 2018−2022. Moreover, the multi-omics techniques for analyzing the interaction mechanism of microbial co culture were briefly introduced. This review aims to provide reference for further research of microbial co-culture and new ideas for microbial medicine development.