Heterocyclic amines (HCAs) are harmful compounds generated during the thermal processing of food, possessing mutagenic and carcinogenic properties that increase the risk of multiple cancers in humans. Therefore, effectively inhibiting the formation of HCAs has long been a research focus in the field of food science. Focusing on research achievements from the past five years, this review systematically analyzes the effects of polyphenolic compounds, polyphenol-rich plant extracts, and spices on the formation of HCAs, as well as the regulatory mechanisms involved. Furthermore, the future development directions of polyphenolic compounds in the mitigation of HCAs are discussed.