This review summarizes current understanding of defensin peptides in skin and hair rejuvenation. It draws on preclinical animal models, mechanistic studies, and human clinical trials, including data on α-defensin and β-defensin formulations. Defensins are discussed in the context of regenerative peptides, growth factor-based cosmeceuticals, extracellular vesicles, safety, regulatory considerations, and heterochronic parabiosis. The goal is to provide facial plastic surgeons and aesthetic clinicians with a practical, evidence-based overview of defensin therapy and its potential integration into regenerative aesthetic practice.