The skin is increasingly recognized as a neuroendocrine organ that continuously communicates with the nervous system, linking cutaneous biology with overall wellness. Despite growing interest in the skin-brain axis, there remains limited synthesis of interventional strategies targeting neuropeptides and neurotransmitters to improve skin health. This systematic review aimed to evaluate the current evidence on neuropeptide- and neurotransmitter-based interventions in dermatology, with a focus on mood-related pathways and cutaneous outcomes. A systematic search of PubMed (January 2015-September 2025) was performed, including interventional studies investigating key neuroendocrine mediators in skin disease and regeneration. A total of 68 studies met inclusion criteria, the majority of which were preclinical, with a smaller proportion of randomized controlled trials. Melatonin, substance P modulation and oxytocin demonstrated the most consistent evidence across anti-inflammatory, reparative and psychodermatologic outcomes. Collectively, these findings position neurohormonal signaling as an emerging therapeutic target in dermatology, with potential applications spanning both disease management and aesthetic medicine.
