Host defense peptides (
HDP
) are multifunctional effectors of the innate immune system, which has antimicrobial and pleiotropic immunomodulatory functions. Although there is a very sophisticated superposition of adaptive immune systems in vertebrates, this system is still essential. As an important family of HDP, cathelicidins are also known for their broad-spectrum antibacterial activity against bacteria, fungi, and enveloped viruses. It has been found in humans and other species, including cattle, pigs, sheep, goats, chickens, rabbits, and some kind of fish. Among them, cathelicidins in birds were described for the first time in 2005. This review focuses on the structure, biological activities, expression, and regulation of avian cathelicidin, especially main effects of host defense cathelicidin on potential therapeutic applications. According to the results obtained both in vitro and in vivo, good perspectives have been opened for cathelicidin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of cathelicidin as novel therapeutic alternatives to antibiotics.