Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a large group of peptide natural products. The remarkably diverse structures and biological activities of RiPPs have sparked a growing interest in their research. Here we report genome mining studies on three classes of RiPPs, including dikarytins, linaridins, and sactipeptides. The biosynthetic mechanisms for some of these RiPPs were investigated by genetic knockout, heterologous expression, and biochemical transformations. These studies highlight the rich biochemistry in forming these structurally diverse peptides. Some of our identified compounds exhibit intriguing antimicrobial activities, and the studies on their mode of action will also be discussed.