Drugs used to treat leprosy such as dapsone (DAP) can result in various adverse effects when administered orally. The disease-causing pathogen has a preferential distribution in peripheral regions of the body and symptoms are manifested primarily in the skin and peripheral nerves. This aspect motivated, in this study, the development of topical formulations containing DAP. Nanoemulsions (NEs) were selected as drug carriers aiming to enhance cutaneous permeation and sustain the drug release. Chaulmoogra oil (CH) was added to the oily nucleus of the NEs considering its history of use in leprosy and its potential healing effect in the skin lesions caused by Mycobacterium leprae. CH effect on formulation characteristics (size, PDI, surface load and stability) and epithelial cell migration was evaluated. CH-based NEs showed to be more monodisperse than NEs without CH (PDI ≤0.26 vs. 0.37). The droplet diameter increased from 189.7 to 227.0 nm when the CH content ranged from 2 to 4%, respectively. Hot-stage analyses and accelerated stability studies revealed that the CH improves both the physical and thermal stability of these nanocarriers. NEs with higher CH content presented greater interaction with the human skin in spectroscopic analyses, which was confirmed by permeation studies. These same formulations increased the amount of DAP retained in the skin (3.40 μg cm−2 in the epidermis and 1.60 μg cm−2 in the dermis) when compared to the nanoemulsion (NE) containing the lowest CH content (2.01 μg cm−2 in the epidermis and 1.06 μg cm−2 in the dermis). Another positive effect is that free and nanoencapsulated CH improved cell migration, which would be useful to treat skin lesions that commonly appear in patients with leprosy. Both free CH and NE provided a wound closure of 70 and 69%, respectively. In summary, the presence of CH is able to improve the anti-leprosy formulation characteristics and provide different benefits to patients. Display omitted