Neurodegenerative diseases (NDs), such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), are major health problems worldwide. To date, available remedies against NDs are limited. In fact, current treatment options include drug intervention and nutritional therapy, which mainly focus on the repair of neuronal damage and functional monitoring. However, these treatments do not completely alleviate disease symptoms. Recently, eliminating harmful molecules, such as reactive oxygen species, and inhibiting neuroinflammation have become potential strategies recommended by many researchers. Accordingly, remarkable interest has been generated in recent years regarding natural products, including polyphenols, that provide neuroprotective effects. In this review, we aimed to provide experimental evidence of the therapeutic potential of punicalagin (PUN), a prevailing compound in pomegranate polyphenols with antioxidant activity. Overall, the chemistry, methods of determination, characteristics of metabolism, transformation mechanisms of action, and neuroprotective effects of PUN on NDs are summarised to provide a scientific basis for elucidating the therapeutic mechanisms and targets of NDs.