The skin's epidermis is an essential barrier as the first guard against invading pathogens, and physical protector from external injury. The skin microbiome, which consists of numerous bacteria, fungi, viruses, and archaea on the epidermis, play a key role in skin homeostasis. Antibiotics are a fast-acting and effective treatment method, however, antibiotic use is a nuisance that can disrupt skin homeostasis by eradicating beneficial bacteria along with the intended pathogens and cause antibiotic-resistant bacteria spread. Increased numbers of antimicrobial peptides (AMPs) derived from humans and bacteria have been reported, and their roles have been well defined. Recently, modulation of the skin microbiome with AMPs rather than artificially synthesized antibiotics has attracted the attention of researchers as many antibiotic-resistant strains make treatment mediation difficult in the context of ecological problems. Herein, we discuss the overall insights into the skin microbiome, including its regulation by different AMPs, as well as their composition and role in health and disease.