Cancer is one of the leading causes of death worldwide, and its high incidence and mortality pose a significant threat to public health. Studies show that more than two-thirds of cancer-related deaths could be prevented through changes in lifestyle, especially dietary patterns. Proanthocyanidins, as a class of polyphenolic compounds widely present in the diet, have attracted wide attention due to their high safety and good biological tolerance. Studies have found that proanthocyanidins have shown multifaceted potential in cancer prevention and treatment. Their mechanisms involve inducing cell apoptosis and cell cycle arrest, improving the tumor immune microenvironment, regulating tumor-related signaling pathways, inhibiting angiogenesis, and suppressing invasion and metastasis, etc. This paper systematically reviews the research mechanisms, different research models, and the development of novel delivery systems of proanthocyanidins in cancer prevention and treatment. It also explores the challenges of current research and future translational directions, providing theoretical basis for promoting the translation of proanthocyanidins from basic research to clinical applications.