Hypothalamic inflammation has been identified as a critical factor driving the development of obesity and associated metabolic disorders. This inflammation-related disruption of energy balance relies on alterations in metabolic cues sensing and hypothalamic cellular functions, together leading to overeating and weight gain. Within the hypothalamic cellular networks controlling energy balance, recent studies have highlighted the significance of glial dysfunction in these processes, suggesting that these cells could provide new avenues for weight loss therapies. Glia rapidly activates following the consumption of a high-fat diet, even after a very short exposure, and contributes to the disruption of the entire system through inflammatory crosstalk. This review explores recent progress in understanding the molecular interactions between glial cells and neurons in hypothalamic inflammation related to obesity, diabetes, and associated complications. Notably, it highlights specialized ependymal cells called tanycytes, whose role is still underestimated in hypothalamic inflammation, and examines the potential for targeting this cell type as a treatment strategy for metabolic disorders.