This study developed a novel Benzoyl Peroxide ethosomal emulgel formulation to enhance drug delivery to the target site of acne vulgaris. Ethosomes, lipid-based nano-carriers containing phospholipids and ethanol, were integrated into an emulgel matrix to improve BPO's penetration through the stratum corneum, the skin's outermost layer. The ethosome emulgel offers hydration, stability, and optimal drug release characteristics. The formulation was evaluated for various parameters, including particle size, skin permeation studies, drug release profile, and stability assessments. The ethosome emulgel showed a higher percentage of entrapment (97%) of (F3) and an ideal average vesicle size (F3). Future clinical investigations are needed to validate its long-term safety, efficacy in diverse patient populations, and comparative effectiveness against existing treatment modalities.