Mitochondrial abnormality is a predominant pathological feature in aging and neurodegenerative diseases including Alzheimer's disease (AD). This chapter reviews AD‐related pathological changes in mitochondrial structure and function and discusses the potential of targeting mitochondria as an effective treatment for the disease. Mitochondrial dysfunction has been implicated in various human pathological conditions such as neurodegenerative diseases. The chapter focuses on how mitochondrial‐targeted therapeutic approaches may be beneficial specifically for AD. Currently, MitoQ and SS31 are the most studied mitochondria‐targeted antioxidants in AD. MitoQ and SS31 have been shown to protect against Aβ toxicity in neurons from an AD mouse model. However, other mitochondrial functions such as Ca²⁺ signaling and mitochondrial respiration also serve as attractive drug targets.