Moenomycins produced by Streptomyces are phosphoglycolipid antibiotics, and inhibit the active sites of peptidoglycan glycosyltransferases involved in the biosynthesis of Gram-positive bacterial cell wall. Moenomycins show a strong biological activity, and possess important research value and development potential. This paper systematically reviews the advances in chemical biology of moenomycins, including the chemical structures, bioactive mechanisms, latest development of biosynthesis, efflux mechanisms and new derivatives of moenomycins. Moreover, the research bottleneck in chemical biology of moenomycins is referred aiming to promote the research and development of high-activity phosphoglycolipid drugs for clinic and industry.