Mushrooms have been an acclaimed food for their unique flavor and medicinal properties since ancient times. Modern research shows that mushrooms are rich in various nutrients and biologically active substances. In recent years, researchers have become increasingly interested in mushrooms because they contain important secondary metabolites, such as phenolic compounds with significant bioactive properties. This review introduces the nutritional components and secondary metabolites in mushrooms, focusing on the bioactive functions and potential applications of mushroom polyphenols. Finally, the current challenges and future research trends of mushroom polyphenols are briefly discussed. In the aspect of nutritional value, mushrooms are high in protein and insoluble fiber, while low in fat and sodium, making them a low-energy, healthy food. Mushrooms contain a large amount of beneficial bioactive substances for health, including phenolic compounds, as well as tocopherols, terpenoids, and phytosterols. Mushroom polyphenols have antioxidant, anti-inflammatory, anti-cancer, anti-tyrosine, antihyperglycemic, and other biological activities beneficial to human health and medical applications, especially in the various degenerative disease and cancer treatments. However, based on the properties of phenolic compounds, research and development in commercial applications still face many issues that need to be addressed by researchers.