Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases with motor disturbances, cognitive decline, and behavioral impairment. It is characterized by the extracellular aggregation of amyloid-β plaques and the intracellular accumulation of tau protein. AD patients show a cognitive decline, which has been associated with oxidative stress, as well as mitochondrial dysfunction. Alpha-lipoic acid (α-LA), a natural antioxidant present in food and used as a dietary supplement, has been considered a promising agent for the prevention or treatment of neurodegenerative disorders. Despite multiple preclinical studies indicating beneficial effects of α-LA in memory functioning, and pointing to its neuroprotective effects, to date only a few studies have examined its effects in humans. Studies performed in animal models of memory loss associated with aging and AD have shown that α-LA improves memory in a variety of behavioral paradigms. Furthermore, molecular mechanisms underlying α-LA effects have also been investigated. Accordingly, α-LA shows antioxidant, antiapoptotic, anti-inflammatory, glioprotective, metal chelating properties in both in vivo and in vitro studies. In addition, it has been shown that α-LA reverses age-associated loss of neurotransmitters and their receptors. The review article aimed at summarizing and discussing the main studies investigating the neuroprotective effects of α-LA on cognition as well as its molecular effects, to improve the understanding of the therapeutic potential of α-LA in patients suffering from neurodegenerative disorders, supporting the development of clinical trials with α-LA.