<p>Skin plays a vital role in protecting the human body from hazardous stimuli such as oxidizing agents and inflammatory triggers. To enhance the skin’s defense mechanisms against both endogenous and exogenous damages, the administration of antioxidants can be a promising strategy. Quercetin (Que) is a well-known flavonoid with prominent antioxidant, anti-inflammatory, anti-aging, anti-cancer, and anti-microbial properties, all of which contribute to improve wound healing and skin care. However, its poor solubility has limited its ability to penetrate the skin effectively. To address this limitation, various formulations and composite strategies have been developed to efficiently increase its cutaneous penetration. In this review, an overview of Que and its derivatives are provided, along with the underlying mechanisms of wound healing, with a focus on the therapeutic capability and performance of Que in every stage of this process. Finally, this review discusses a range of drug delivery vehicles, such as nanoparticles, hydrogels, and electrospun nanofibers, which promote the transdermal penetration of Que. Overall, Que and its advanced delivery systems provide new insights for translation into clinical wound management, offering novel therapeutic avenues for both cosmeceutical and therapeutic applications in skin repair and regeneration.</p>