Brucine (BRU) is a natural product derived from nux-vomica seeds. It is commonly used as an anti-inflammatory and anti-nociceptive drug to relieve arthritis and traumatic pain. Nevertheless, its use is significantly limited by its low aqueous solubility, as well as the gastrointestinal problems and systemic toxicity that may occur following oral administration. The goal of this study, therefore, was to formulate and evaluate a nanoemulgel formulation of BRU for enhanced topical anti-inflammatory and anti-nociceptive activities. Different formulations were developed (BRU gel, emulgel and nanoemulgel) using 1% w/w NaCMC as a gelling agent. The formulated preparations were assessed for their physical appearance, spreadability, viscosity, particle size, in vitro drug release and ex vivo permeation studies. In addition, the carrageenan-induced rat hind paw edema method was adopted to scrutinize the anti-inflammatory activity, while the hot plate method and acetic acid-induced writhing test were used to assess the anti-nociceptive activity of different formulations in male BALB/c mice. The formulated BRU-loaded preparations showed good physical characteristics. Cumulative drug release from BRU-loaded nanoemulgel was remarkably higher than that of the other formulations. Ex vivo drug permeation of the nanoemulgel formulation across rat skin showed enhanced drug permeation and higher transdermal flux as compared to BRU-loaded gel or emulgel. Most importantly, the carrageenan-induced rat hind paw edema model verified the efficient anti-inflammatory potential of BRU-loaded nanoemulgel. In addition, BRU-loaded nanoemulgel exhibited significant protective effects against thermal stimulation in the hot plate test and remarkably inhibited acetic acid-induced abdominal writhing in mice. Furthermore, a skin irritation test indicated that BRUloaded nanoemulgel elicited neither edema nor erythema upon application to rat skin. Collectively, our results suggest that myrrh oil-based nanoemulgel might represent a promising delivery vehicle for potentiating the antiinflammatory and anti-nociceptive actions of brucine.