Aim: The impacts of zinc oxide nano-extract from Origanum majorana leaves on the liver histological morphology of rats were investigated in the current study. Materials and Methods: There were forty-two rats that are rats are divided into six groups of seven animals. Performing the experiment, 0.5 mg of normal saline was given to the first group, T1. Additionally, a 10 mg/kg nano-extract of Origanum majorana leaves was given to the second group, T2. A nano-extract solution containing 15 mg/kg of Origanum majorana leaves extract was injected to the third group, T3. A nano-extract derived from the seeds of Origanum majorana leaves of 10 mg/kg in combination with L. donovania was injected to the fourth group, T4. A nano-extract from Origanum majorana leaves at a concentration of 15 mg/kg in conjunction with L. donovania was injected to the fifth group, T5. Finally, L. donovania alone was injected for 29 days to the sixth group, T6. Results: Considerable changes were noticed in the nucleus and fib. Moreover, the findings revealed that there are several changes in their liver’s structure like sinusoidal dilatation, prescience of specific inflammatory cells surrounding the central vein, and prescience of simple necrosis and bleeding in L. dono vani- infected tissue. Conclusions: The histological changes on the liver treated with Nano-extract (zinc oxide) of the Origanum majorana leaves at different concentrations was employed for treating the histological shifts and reducing the damage caused by the parasite. Thus, effectiveness of the nano-extract is effective in reducing the influences and resisting the parasite.