Ultraviolet (UV), as the most common environmental stress factor to human skin, causes redox imbalance and leads to photoaging and the development of cancer. In this work, we screened a nonapeptide (PWH) with good activities of antioxidant, promoting the secretion of type 1 collagen (COL-1) and repairing damaged skin from a series of rationally designed novel short peptides. PWH could alleviate UV-A-induced oxidative stress, restrain pro-inflammatory cytokine production, protect mitochondrial function, and maintain autophagy activity. We also first indicated that inhibiting the PI3K/AKT/mTOR signaling pathway and restoration of autophagy activity might delay the photoaging process in skin cells. Topical applications of PWH were further demonstrated to exhibit significant protection in full-wavelength UV-induced skin aging in mice models both in the prophylaxis and treatment way. In addition, given the good stability and without unwanted toxicity and anaphylaxis, PWH could be a promising candidate for cosmetics and pharmaceuticals.