Core Viewpoint - The article systematically reviews the global development history of peptide research, particularly focusing on skin-active peptides, their discovery, mechanisms, clinical applications, and future research directions, highlighting significant milestones and breakthroughs in the field [3][7][43]. Development History of Peptides - The concept of "peptide" was first proposed by Hermann Emil Fischer in 1902, laying the foundation for peptide chemistry and subsequent research in skin-active peptides [9][10]. - In 1922, insulin became the first peptide drug extracted from animal pancreas, demonstrating the biological activity and therapeutic potential of peptides [11]. - The 1950s saw significant breakthroughs in peptide synthesis techniques, including the total synthesis of oxytocin and vasopressin, which opened new avenues for peptide production [12][13]. Key Discoveries and Applications - The discovery of GHK-Cu (blue copper peptide) in 1973 marked a turning point in skin-active peptide research, proving the biological basis for small peptides in skin regulation and repair [17]. - The introduction of palmitoyl tripeptide-1 and palmitoyl hexapeptide-12 in 1992 represented a shift towards biomimetic signaling functions in cosmetic applications [29][31]. - The 2000s saw the emergence of neuropeptide inhibitors like acetyl hexapeptide-3, which mimic the effects of botulinum toxin without the need for injections, becoming popular in anti-aging products [33]. Current Research Trends - AI-assisted peptide design and transdermal delivery technology are at the forefront of current research, significantly shortening development cycles and improving delivery efficiency [37][38]. - The use of enzymatic hydrolysis and recombinant DNA technology has become prevalent in producing bioactive peptides, enhancing the feasibility of large-scale production [28][39]. Future Directions - Future research is expected to focus on overcoming challenges related to synthesis complexity, stability, and regulatory compliance, with an emphasis on personalized skincare solutions based on individual skin characteristics [45][47]. - The rise of Chinese research teams, exemplified by Han Shu's development of ring hexapeptide-9, signifies a growing presence in the global peptide market, showcasing innovation in cosmetic ingredients [39][41][42].