Aim of the study is to formulate and evaluate Mebendazole nanoemulsion containing Oregano essential oil, for enhancing anthelmintic activity prepared by spontaneous emulsification method followed ultrasonication. A problem stated with the use of synthetic anthelmintics is the development of parasitic resistance, which threaten the success of treatment in humans, use of a herbal alternative may reduce such resistance. Essential oil of Oreganum vulgare is taken orally kills intestinal parasites, therefore it can enhance the action potential of anthelmintics. Nanoemulsion was formulated using a Pseudo ternary phase diagram, which was created using design expert software 9.0.5.1. Out of the five phase diagrams ratio of 1:3 was chosen, since it shows maximum area in the overlay plot. Nanoemulsion containing drug (NE1), containing drug and oregano essential oil (NE2) and oregano oil (NE3) were prepared using smix ratio 1:3. Anthelmintic activity, viscosity and globule size were fixed as the parameters for optimisation.NE2 was selected as the optimised formulation having viscosity (18.61±0.45Cp), Globule size (36.24µm), polydispersity index (0.2). NE 2 showed a minimum mean time of paralysis (1.2±0.01min) and mean time of death (2.2±0.02 min). Reduction in time for paralysis and death may be an indication of the synergistic effect of oregano essential oil on anthelmintic activity of Mebendazole. Evaluations of anthelmintic activity was carried out in artificial laboratory conditions by using the earthworms (Lumbricusterrestris).This study suggest that nanoemulsion is a promising novel formulation that can enhance the solubility of poorly soluble drug like Mebendazole and thereby enhance its oral bioavailability.