The bare and moist characteristics of amphibian skin makes it prone to microbial infection. In order to resist the invasion of pathogenic microorganisms, amphibians form an immune system with antimicrobial peptides as the main defense effector during the long-term natural evolution. Antimicrobial peptides (AMPs) are widely distributed in animals, plants and microorganisms, which are pivotal weapons for host to resist bacteria, fungi, viruses and protozoa. AMPs represent very ancient and effective natural defense substances in evolution. Cathelicidins are an important family of AMPs exclusively existing in vertebrates, and they are also one of the most powerful family of AMPs known to date. Cathelicidins have been identified in most kinds of vertebrates. In addition to potent and broad-spectrum antimicrobial activities, they also possess many other important activities such as anti-inflammation, anti-oxidation, wound repair, tissue damage inhibition and angiogenesis promotion. As a result, Cathelicidins are becoming a hot spot of anti-infective peptide agent development. There is a large amount of amphibian species in nature, which contain many novel Cathelicidins family AMPs with diverse structures and functions. Therefore, it is of great significance to study amphibian Cathelicidins for animal immunology research and drug development. The present article comprehensively reviews the research progress of amphibian Cathelicidins from the aspects of general characteristics, source distribution, biosynthesis and structures, biological activities, mechanisms of action and application prospects.