Polyphenols are immunonutrients that modulate immunometabolism in chronic diseases. They act through multiple mechanisms, including nutrient sensing, AMPK/mTOR signaling, and mitochondrial biogenesis. Polyphenols can shift immune cells towards a less inflamed, tolerogenic phenotype by modulating metabolic pathways and epigenetic reprogramming. They also influence chromatin remodeling and coordinate both epigenetic and metabolic reprogramming. Polyphenols have been shown to modulate innate and adaptive immunity by affecting dendritic cells, macrophages, neutrophils, and natural killer cells. They can suppress inflammatory responses, enhance antigen presentation, and promote immune tolerance. Polyphenols also influence T and B cells by modulating their differentiation and function. In immunometabolic diseases, polyphenol-based immunonutrition has the potential to improve immune function and reduce chronic inflammation. The study highlights the importance of polyphenols in immunometabolism and their potential as therapeutic agents in chronic diseases. The research emphasizes the need for further studies to translate polyphenol-based immunonutrition into clinical practice.Polyphenols are immunonutrients that modulate immunometabolism in chronic diseases. They act through multiple mechanisms, including nutrient sensing, AMPK/mTOR signaling, and mitochondrial biogenesis. Polyphenols can shift immune cells towards a less inflamed, tolerogenic phenotype by modulating metabolic pathways and epigenetic reprogramming. They also influence chromatin remodeling and coordinate both epigenetic and metabolic reprogramming. Polyphenols have been shown to modulate innate and adaptive immunity by affecting dendritic cells, macrophages, neutrophils, and natural killer cells. They can suppress inflammatory responses, enhance antigen presentation, and promote immune tolerance. Polyphenols also influence T and B cells by modulating their differentiation and function. In immunometabolic diseases, polyphenol-based immunonutrition has the potential to improve immune function and reduce chronic inflammation. The study highlights the importance of polyphenols in immunometabolism and their potential as therapeutic agents in chronic diseases. The research emphasizes the need for further studies to translate polyphenol-based immunonutrition into clinical practice.