Hormones can interact with mitochondria in various ways, modulating their biogenesis, dynamics, metabolism, respiration and stress response. Some studies suggest that sex hormones, such as estrogen and testosterone, can exert neuroprotective effects by improving mitochondrial function and reducing oxidative stress in the brain. However, the molecular and cellular mechanisms by which hormones regulate mitochondria are not fully elucidated, as well as the effects of hormonal decline on mitochondrial function during endocrine aging and menopause. Our goal is to fill this knowledge gap, using a multidisciplinary approach that combines experimental models in silico, in vitro and in vivo, as well as clinical samples from patients with different hormonal and cognitive profiles.