The wound healing’s acceleration depends on developing an innovative therapeutic strategy that reduces inflammation, regulates oxidative stress, promotes fibroblast proliferation, and collagen deposition. This study aimed to prepare and evaluate a green nanoemulsion-based formulation containing propolis, tea tree, and jojoba oils to integrate their biological activities for enhanced wound healing efficacy. Nanoemulsion formulations were prepared via a low-energy emulsification approach and characterized by zeta potential, hydrodynamic size (DLS), polydispersity index (PDI), and transmission electron microscopy (TEM). The in vitro antioxidant and anti-inflammatory activities were assessed. In addition, cytotoxicity was assessed using the MTT colorimetric assay against the HSF-1 normal skin cell line. Additionally, NO and IL-1β levels were measured on NHDF-Ad cells. A propolis nanoemulgel (PNEG) was produced using Carbopol 940 as a gelling agent. The in vivo wound healing efficacy of PNEG was tested by evaluating wound closure rate, malondialdehyde, superoxide dismutase, tumor necrosis factor-alpha, and histopathological alterations in healed tissues. The obtained results demonstrated that, the optimized formula displayed a zeta potential of − 28.6 ± 1.91 mV, a DLS of 187.8 ± 3.29 nm, and a 50% cytotoxic concentration (CC 50 ) of 24.82 ± 0.16% and showed a significant antioxidant and anti-inflammatory activities. Furthermore, NO and IL-1β levels were significantly decreased by 35% and 40%, respectively, demonstrating potent anti-inflammatory activity. Additionally, the therapeutic activity was associated with inhibition of IL-1β /NO-driven inflammatory signaling, suppression of NF-κB , activation of the NRF2/HO-1 antioxidant axis, and modulation of BAX/Bcl-2 apoptotic pathways. The in vivo results indicated that PNEG accelerates wound closure significantly compared with both positive and negative control groups. SOD level increased significantly ( p < 0.05), whereas MDA and TNF-α levels decreased compared with the control groups ( p < 0.05). Furthermore, histopathological examination illustrated infiltration reduction of inflammatory cells, increased collagen deposition, and fast epithelialization. The developed green formula, resulting from both the low-energy, environmentally friendly preparation method and the natural origin of its constituents, was demonstrated to be an antioxidant and inflammatory and to accelerate wound healing, suggesting it could be used as a natural formula for topical wound healing application.