Alzheimer’s disease (AD), a chronic and progressive neurodegenerative disease, is characterized by memory and cognitive impairment and by the accumulation in the brain of abnormal proteins, more precisely beta-amyloid (β-amyloid or Aβ) and Tau proteins. Studies aimed at researching pharmacological treatments against AD have focused precisely on molecules capable, in one way or another, of preventing/eliminating the accumulations of the aforementioned proteins. Unfortunately, more than 100 years after the discovery of the disease, there is still no effective therapy in modifying the biology behind AD and nipping the disease in the bud. This state of affairs has made neuroscientists suspicious, so much so that for several years the idea has gained ground that AD is not a direct neuropathological consequence taking place downstream of the deposition of the two toxic proteins, but rather a multifactorial disease, including mitochondrial dysfunction as an early event in the pathogenesis of AD, occurring even before clinical symptoms. This is the reason why the search for pharmacological agents capable of normalizing the functioning of these subcellular organelles of vital importance for nerve cells is certainly to be considered a promising approach to the design of effective neuroprotective drugs aimed at preserving this organelle to arrest or delay the progression of the disease. Here, our intent is to provide an updated overview of the mitochondrial alterations related to this disorder and of the therapeutic strategies (both natural and synthetic) targeting mitochondrial dysfunction.