<p>Avocado oil is a nutraceutical that offers multiple health benefits due to its rich composition of fatty acids. Avocado’s antioxidant molecules can protect from neuronal damage, potentially preventing or slowing down the onset of neurodegenerative diseases. Within the search for therapeutic targets in neurodegenerative conditions, we focused on testing the neuroprotective effect of the components contained in avocado oil in a Huntington’s disease (HD) model. Quinolinic acid (QA) is a potent striatal excitotoxin that leads to axon-sparing neurodegeneration and induces N-methyl-D-aspartate receptor-mediated cytotoxicity and neuroinflammation. The QA-lesioned rat striatum shares similarities with the neostriatum observed in individuals with HD. This work aimed to study the neuroprotective effects of an avocado oil-supplemented diet on the QA model by measuring neurological and oxidative damage. For this purpose, Wistar rats were fed with an avocado oil-supplemented diet for 20 days. First, evaluated blood biochemical parameters (glucose, cholesterol, and triglycerides) in the blood and testing liver function by the determination of hepatic enzymes levels in plasma and verifying that the avocado oil-supplemented diet did not affect either. Additionally, a second set of rats were fed with an avocado oil-supplemented diet and then lesioned with QA. Our results show that avocado oil supplementation reduces oxidative damage, prevents neurological damage by reducing the ipsilateral turns by maintaining the levels of striatal GABA content, and reduces striatal neurodegeneration assessed by Fluoro-Jade^® B. These results suggest that an avocado oil-supplemented diet has a potential role in reducing the negative effects observed in the HD model of the QA intrastriatal administration.</p>