Obesity is a significant health concern affecting 13% of the world’s population. It is often associated with insulin resistance and metabolic-associated fatty liver disease (MAFLD), which can cause chronic inflammation in the liver and adipose tissue. Obese hepatocytes show increased lipid droplets and lipid peroxidation, which can lead to the progression of liver damage. Polyphenols have been shown to have the ability to reduce lipid peroxidation, thereby promoting hepatocyte health. Chia leaves, a by-product of chia seed production, are a natural source of bioactive antioxidant compounds, such as cinnamic acids and flavonoids, which have antioxidant and anti-inflammatory properties. In this study, chia leaves’ ethanolic extracts of two seed phenotypes were tested on diet-induced obese mice to evaluate their therapeutic potential. Results show that the chia leaf extract positively affected insulin resistance and lipid peroxidation in the liver. In addition, the extract improved the HOMA-IR index compared to the obese control group, reducing the number and size of lipid droplets and lipid peroxidation. These results suggest that chia leaf extract may help treat insulin resistance and liver damage associated with MAFLD.