Impact of an innovative antioxidant wall material, vanillic acid-grafted chitosan, on enhancement of oxidative stability was investigated. Microencapsulation with the aid of spray drying was proven to be an effective method for preserving omega-3 fatty acids. Streptozotocin-induced diabetic rats were used to examine the effects of microcapsules loaded with sardine oil and vanillic acid-grafted chitosan (SO-MC) as wall material. Antioxidant and anti-hyperglycemic effects were significantly enhanced in rat models treated with 500 mg/kg of SO-MC. The lack of aberrant weight fluctuations or mortality in an acute toxicity assessment indicated that there were no symptoms of toxicity. Addition of SO-MC into the meal resulted in dose-dependent decreases in blood glucose levels as compared to the diabetes control group. Treatment with SO-MC reduced lipid peroxidation, whereas increased production of glutathione peroxidase (GPx) and glutathione S-transferase (GSH), two crucial antioxidants, as compared to the diabetes control group. These findings underscore the potential utility of SO-MC as a promising dietary supplement for the management of hyperglycemia