Diabetic encephalopathy (DE) is a debilitating complication of diabetes mellitus, characterized by cognitive decline, memory impairment, and mood disturbances. Despite its significance, there is a lack of effective therapeutic strategies to address this condition. Isoflavones, a class of plant-derived compounds, have been shown to exhibit neuroprotective and antioxidant properties, making them promising candidates for the treatment of DE. In this study, we investigated the in vivo efficacy of isoflavones loaded nanodroplets (IND) for the treatment of DE. Male Sprague-Dawley rats were induced with streptozotocin to develop type 1 diabetes mellitus, followed by injection of INL or vehicle control. The rats were then evaluated for cognitive function, memory, and mood disturbances using a battery of behavioral tests. Additionally, we assessed the changes in brain morphology and biochemistry using magnetic resonance imaging (MRI) and Western blot analysis.Our results show that IND significantly improved cognitive function, memory, and mood disturbances in diabetic rats compared to vehicle control. IND also reduced oxidative stress and inflammation in the brain, as evidenced by decreased levels of malondialdehyde and tumor necrosis factor-alpha (TNF-alpha). Furthermore, IND increased the expression of brain-derived neurotrophic factor (BDNF) and reduced the expression of cleaved caspase-3, indicating enhanced neuroprotection. These findings demonstrate the therapeutic potential of IND in the treatment of DE. The nanodroplet delivery system allows for targeted and sustained release of isoflavones to the brain, which may improve their bioavailability and efficacy. Our study provides a novel therapeutic approach for the treatment of DE, and further research is needed to explore the long-term efficacy and safety of IND in human subjects.