According to the World Health Organization (WHO), dementia is a syndrome that affects thoughts, memory, the ability to perform day-to-day activities, and behavior. Alzheimer's disease (AD) corresponds to almost 70% of dementia cases, affecting mainly the elderly over 60 years old, causing physical, psychological, social, and economic impacts. Whether of natural or synthetic origin, the polyphenols and their derivatives have great versatility in terms of biological activity, as can be seen in the literature, exhibiting different properties, such as anti-inflammatory, anti-tumor, anti-viral, anti-microbial, and others. Among therapeutic alternatives are polyphenols and their derivatives as a molecular class broadly studied against neurodegenerative diseases, including AD. This chapter consists of a literary review of some polyphenols and derivatives with proven activity against AD, thus showing their importance among the other molecular classes, when it comes to proposing new bioactive agents against AD. Many targets are studied for this disease, since the pathogenesis of AD requires clarification and approved drugs only delay the evolution of the disease, such as donepezil hydrochloride, galantamine, among others. In addition to encouraging new studies by relating polyphenols and derivatives targeting AD, this work can assist research groups by providing some recent studies that have proven this relationship. At the end of this research, it is possible to realize the importance and applicability of these compounds in AD.