Diabetes and mood disorders are intricately interconnected, with each condition elevating the risk of the other. This bidirectional relationship, further exacerbated by neuroinflammation, fosters an environment conducive to the development of anxiety and depression. Glucagon-like peptide-1 receptor agonists, such as semaglutide, offer promising therapeutic options that not only target type 2 diabetes but also can positively influence mood. Our study's primary goal was to evaluate the effectiveness of semaglutide, in mitigating anxiety and depression within an animal model of diabetes. The neuroprotective properties of semaglutide were evaluated by examining its influence on the kynurenine pathway and neurobiological markers (GFAP, NEFL, NSE, and GAL3) in the perfrontal cortex, selected for its key role in cognitive function and emotional regulation, impaired in diabetes and mood disorders. Additionally, we examined semaglutide's impact on peripheral inflammation and stress parameters to elucidate its role in modulating systemic inflammatory responses linked to mood disorders. Additionally, we conducted behavioral assessments to better understand how semaglutide influences anxiety and depression-related behaviors in diabetic mice. Semaglutide therapy significantly improved behavioral patterns and neurochemical markers in diabetic mice. The frequency of administration significantly influenced the outcomes, whereas the dosage appeared to have a limited impact. Here we show that semaglutide expands its therapeutic potential beyond diabetes, significantly influencing mood disorders through neuroinflammatory pathways. Semaglutide has the potential to be a key element in formulating integrated treatment strategies that address both metabolic health and mental well-being, ultimately enhancing the quality of life for individuals navigating these interrelated challenges.