Curcumin and emu oil derived from emu bird (Dromaius novaehollandiae) has shown promising results against inflammation. However, the delivery of curcumin is hindered due to low solubility and poor permeation. In addition, till date the role of emu oil in drug delivery has not been explored systemically. Hence, the current investigation was designed to evaluate the anti-inflammatory potential of curcumin in combination with emu oil from a nanoemulgel formulation in experimental inflammation and arthritic in vivo models. Nanoemulsion was prepared using emu oil, Cremophor RH 40 and Labrafil M2125CS as oil phase, surfactant and co-surfactant. The optimized curcumin loaded nanoemulsion with emu oil was incorporated into carbopol gel for convenient application by topical route. The anti-inflammatory efficacy was evaluated in carrageenan induced paw edema and FCA induced arthritic rat model in terms of paw swelling, weight indices of the liver and spleen, pathological changes in nuclear factor kappa B, iNOS, COX-2 expression and inflammatory cytokines. Arthritic scoring, paw volume, biochemical, molecular, radiological and histological examinations indicated significant improvement in anti-inflammatory activity with formulations containing curcumin in combination with emu oil compared to pure curcumin. These encouraging results demonstrate the potential of formulations containing curcumin and emu oil combination in rheumatoid arthritis.