Medium- and long-chain free fatty acids are not only an important source of energy for the body, but also important signal molecules in the body’s immunity. Recent studies have shown that medium- and long-chain free fatty acids interact with free fatty acid receptors (FFARs) 1 and 4 to regulate insulin secretion and inflammation and in turn the body’s immune system and metabolism. In this review, we discuss the nutritional role and metabolism of dietary medium- and longchain free fatty acids in the body, focusing on the latest progress in understanding the key physiological functions of medium and long-chain free fatty acids and their receptor-mediated signal pathways in taste signal transduction, metabolic regulation, and immune response and in research on synthetic agonists of FFAR1 and FFAR4.