The current study aimed to create a metronidazole nanoemulsion and then use it in the treatment of skin lesions in mice caused by Entamoeba histolytica. We used parasite isolates which taken from the Department of Biology, College of Science, University of Kirkuk. It was rediagnosed by conventional methods. After prepared metronidazole nanoemulsion. We selected 24 healthy males Mus musculus with an average weight of 20-25 grams mice aged 9-12 weeks from, the animals were randomly divided into four groups, with six animals in each group, as follows Control group which injected with normal saline in a volume of 0.1 ml. The second group was injected with a suspension of E. histolytica in a volume of 0.1 ml and at a concentration of 1 x 108 CFU. The third group was injected with Mt-nanoemulsion 0.1 ml. The fourth group was injected with a suspension of E. histolytica and treated with Mt-nanoemulsion. The solubility investigation was conducted using a variety of vehicles to determine the optimal solvent for isradipine's dissolution. Pseudo ternary phase diagrams are created at surfactant and co-surfactant mix related ratios of (1:1, 1:2, 1:3, 1:4, and 2:1). Eight nano emulsions were created by combining several amounts of (Transcutol, Tween20, and Triacetin). The findings indicated that Triacetin was included in the formulations to preserve the medication in a solubilized state and prevent precipitation of the drug because Triacetin had a better solubility of metronidazole. The results of the in vitro study showed that the levels of Malondialdehyde were substantially greater (P >0.05) in the E. histolytica group than in the normal mouse group. Glutathione and catalase levels in the E. histolytica group were substantially lower (P>0.05) than those of normal mice. MDA, GSH, and catalase levels did not differ significantly between the Mt-nanoemulsion-treated group and the control group (P<0.05).