As natural bioactive compounds obtained from the daily diet, plant polyphenols have shown potential in anti-aging research to exert their effects through multi-target regulatory networks, such as the AMPK/SIRT1 axis and inflammatory and oxidative stress pathways. However, their oral bioavailability is quite low, which has become a major obstacle limiting their progression towards clinical application. This review provides a systematic overview of progress in this field and further explores the potential applications of plant polyphenols in supportive cancer therapy through their intervention in the aging process. It notes that although current research is becoming increasingly detailed in its exploration of mechanisms, there remain widespread shortcomings, such as insufficient physiological relevance and relatively weak clinical evidence. Future work should focus more on validating mechanisms in physiologically relevant models and promoting the design of more rigorous clinical trials; only then can plant polyphenols truly be transformed from laboratory potential into tangible clinical benefits.