Polydatin (PD) is a natural single‐crystal product that is primarily extracted from the traditional plant Polygonum cuspidatum Sieb. et Zucc. Early research showed that PD exhibited a variety of biological activities. PD has attracted increasing research interest since 2014, but no review comprehensively summarized the new findings. A great gap between its biological activities and drug development remains. It is necessary to summarize new findings on the pharmacological effects of PD on current diseases. We propose that PD will most likely be used in cardiac and cerebral ischaemia/reperfusion‐related diseases and atherosclerosis in the future. The present work classified these new findings according to diseases and summarized the main effects of PD via specific mechanisms of action. In summary, we found that PD played a therapeutic role in a variety of diseases, primarily via five mechanisms: antioxidative effects, antiinflammatory effects, regulation of autophagy and apoptosis, maintenance of mitochondrial function, and lipid regulation.