<p>Obesity is closely related to liver disease. However, few studies have focused on the impact of adipose tissue-derived extracellular vesicles (EVs) in obesity on liver disease. Therefore, we aimed to investigate the effect of adipose tissue-derived EVs from high-fat diet (HFD)-fed obese mice (EV-HFD) on liver damage induced by oxidative stress. We investigated alterations in the expression of antioxidant enzymes in adipose tissue, and the loading of those enzymes into adipose tissue-derived EVs. Furthermore, we treated alpha mouse liver 12 (AML12) cells with adipose tissue-derived EVs and induced oxidative stress. We observed that the HFD did not exert an effect on the protein expressions of antioxidant enzymes in adipose tissue. Intriguingly, the EV-HFD exhibited an upregulation in the loading of catalase (CAT) when compared to the adipose tissue-derived EVs from normal chow-fed mice (EV-NC). Notably, both types of EVs exhibited a similar capacity to mitigate cell damage when exposed to oxidative stress. Our findings indicate that obesity-induced loading of more CAT into adipose tissue-derived EVs cannot improve their antioxidant capacity in AML12 cells. We suggest that adipose tissue-derived EVs can serve as a tool to maintain homeostasis and defend against oxidative stress, thereby supporting normal physiological functions.</p>