<p>Pomegranate peels, a valuable waste byproduct, aligned with the Sustainable Development Goals by United Nations offering a possibility for use as a raw material in herbal formulations. The review aims to highlight the pharmaceutical importance of pomegranate peel bioactive compounds and their applications in the skincare industry. A systematic search of studies identified through scientific databases resulted in the PRISMA chart. Additionally, an exhaustive search using keywords such as pomegranate peel, skincare, ADME, nanoparticles, therapeutics, and bioactive compounds led to a bibliometric analysis. The peels support the waste-to-wealth concept with a rich repertoire of flavonoids, including quercetin, kaempferol, and catechin, as well as polyphenolic compounds and other tannin compounds, such as punicalagin and ellagic acid. These compounds serve as natural reducing agents for synthesizing various nanoparticles and unveiling therapeutic activities, including antibacterial, anti-inflammatory, anticancer, and antioxidant properties. Furthermore, an attempt to bridge the gap by examining the pharmacokinetic studies on key bioactive compounds identified through ADME analysis, supported the transdermal and topical applications of these compounds. The profiling suggests that tannin compounds, such as punicalagin, have low skin permeability, indicating potential roles in topical applications. In contrast, ellagic acid exhibits high skin permeability, suggesting possible applications in products such as sunscreens. The combinatorial formulation, consisting of pomegranate peel-derived nanoparticles, has potential additional benefits by facilitating skincare products with photoprotection, enhanced hydration, and topical applications. The study also calls for future research focused on clinical validation and scalable commercial applications.</p> Graphical Abstract <p></p>