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Natural products have played indispensable roles in drug development and biomedical research. Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a group of fast-expanding natural products attribute to genome mining efforts in recent years. Most RiPP natural products were discovered from bacteria, yet many eukaryotic cyclic peptides turned out to be of RiPP origin. This review article presents recent advances in the discovery of eukaryotic RiPP natural products, the elucidation of their biosynthetic pathways, and the molecular basis for their biosynthetic enzyme catalysis.