Wound healing involves a series of complex bioprocesses, including repairing skin damage, maintaining its barrier features, and preserving all other skin functions. Since the skin is the primary organ exposed to external factors, these bioprocesses can be interrupted by potential exogenous toxicants. Efforts to mitigate the effects of these toxicants can help accelerate the healing process, facilitating complete wound recovery. In this context, sumac () extract, rich in polyphenolics with antioxidant and anti-inflammatory properties, can be exploited to overcome oxidant and inflammation-dependent burdens. Ethosomes, lipid-based intradermal delivery vehicles, have been selected for the delivery of sumac extract, as they enhance penetration through the skin layers. Considering their remarkable flexibility and deformability, ethosomes can minimize drug leakage even under harmful penetration conditions. Given the diverse bioactive content of sumac extract, ethosomes have been considered ideal for delivering both hydrophilic and lipophilic active compounds. Sumac extract (SuExt)-loaded ethosomes (SuExt-ethosomes) were therefore produced and characterized. These nanocarriers demonstrated significant cellular internalization and cytocompatibility in human dermal fibroblasts (HDFs), along with excellent antioxidant and anti-inflammatory activity. A comprehensive investigation, supported by proteomic analysis, revealed that SuExt-ethosomes present promising wound healing potential, supporting future investigations in preclinical models.