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This Special Issue is focused on natural polyphenols and their synthetic bioactive analogues. It is composed of one review on aza- and azo-stilbenes as bioisosteric analogs of the stilbenoid resveratrol and four original articles, including studies on synthetic (bisphenol neolignans inspired by honokiol, multicomponent synthesis of polyphenols), and natural polyphenols (polyphenols from Tamarix ramosissima and Melanoleuca styphelioides) as antiproliferative, anti-Alzheimer's, antioxidant, antimicrobial, or anti-inflammatory agents.