Huge epidemiological and clinical studies have confirmed that black tea is a rich source of health-promoting ingredients, such as catechins and theaflavins (TFs). Furthermore, TF derivatives mainly include theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin-3′-gallate (TF2B), and theaflavin-3,3′-digallate (TF3). All of these TFs exhibit extensive usages in pharmaceutics, foods, and traditional medication systems. Various indepth studies reported that how TFs modulates health effects in cellular and molecular mechanisms. The available literature regarding the pharmacological activities of TFs has revealed that TF3 has remarkable anti-inflammatory, antioxidant, anticancer, antiobesity, antiosteoporotic, and antimicrobial properties, thus posing significant effects on human health. The current manuscript summarizes both the chemistry and various pharmacological effects of TFs on human health, lifestyle or aging associated diseases, and populations of gut microbiota. Furthermore, the biological potential of TFs has also been focused to provide a deeper understanding of its mechanism of action.