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Background and Objectives: Nanomedicine is a constantly growing field for the diagnosis and treatment of various diseases as well as for regenerative therapy. Nanotechnology-based drug-delivery systems improve pharmacological and pharmacokinetic profiles of plants based biologically active molecules. Based on traditional claims, leaves of the Tamarix aphylla (TA) were investigated for their potential healing activity on burn wounds. Materials and Methods: In this study, TA-based nanoemulsion was prepared. The nanoemulsion was characterized for size, zeta potential, pH, viscosity, and stability. The nanoemulsion containing plant extract was converted into cream and evaluated for its efficacy against acid-burn wounds inflicted in the dorsum of rabbits. The animals were classified into four main groups: Group A as a normal control group, Group B as a positive control (treated with cream base + silver sulfadiazine), Group C as a standard drug (silver sulfadiazine), and Group D as a tested (treated with nanoemulsion cream containing TA extract). The prepared system could deliver TA to the target site and was able to produce pharmacological effects. On days 0, 7, 14, 21, 28, and 35, wound contraction rate was used to determine healing efficacy. The wound samples were collected from the skin for histological examination. Results: Based on statistical analysis using wound-healing time, Group D showed a shorter period (21.60 ± 0.5098) (p < 0.01) than the average healing time of Group C (27.40 ± 0.6002) (p < 0.05) and Group B (33.40 ± 0.8126) (p < 0.05). The histopathological assessment showed that burn healing was better in Group D compared with Group C and Group B. The nanoemulsion cream had a non-sticky texture, low viscosity, excellent skin sensations, and a porous structure. By forming a protective layer on the skin and improving moisture, it enhanced the condition of burnt skin. Conclusions: According to the findings of this study, nanoemulsion cream containing TA extract has great potential in healing acid-burn wounds