High-sucrose high-fat diets are one of the causes of malnutrition, and may induce metabolic alterations such as dyslipidemia, insulin resistance, and adipogenesis. The objective of this work was to investigate the possible protective effect of traditionally edible avocado creole peel (Persea americana Mill var. drymifolia) when consuming a high-sucrose and fat diet (HSFD). The experimental animal model included 21 male Wistar rats divided in three groups: the control group received a standard diet of purina®, the HSFD group received a high fat diet plus 30% sucrose in drinking water, and finally the HSFD + AP group received the HSFD diet supplemented with 200 mg/kg of avocado peel for 14 weeks. It was observed that alterations included higher cholesterol, glucose, insulin, fatty acids and TNF-α levels as well as lower HDL, and adiponectin. The addition of avocado peel reverted some of these effects, resulting in normal values of triglicerides, insulin and adiponectin, while attenuated the levels of total cholesterol. Liver weight of the group added with avocado peel was similar to the control group. The neuronal density in the hippocampal areas CA1 and dentate gyrus DC were lower in the high glucose fat group, while the ingestion of the avocado peel showed a neuroprotective effect. The avocado creole ingestion reverted or attenuated most of the metabolic effects caused by a high-sucrose fat diet which was attributed to the compounds detected by HPLC-MS and GC-MS that included bioactive polyphenols such as flavanol quercetin, flavanone naringenin, flavan 3-ol catechin, cyanidin 3-glucoside, pelargonidin 3-glucoside, pelargonidin 3-rhamnoside, hydroxydelphinidin, eugenol and estragole.