Evidence indicates that short-chain fatty acids (SCFAs) generated from the gut microbiota play crucial roles in host metabolism. They contribute to metabolic regulation and energy acquisition of the host by influencing the development of metabolic disorders. This review aims to synthesize recent advances from the literature to investigate the implication of SCFAs in the modulation of obesity and diabetes pathologies. For a better understanding of the relationships between SCFAs and host metabolism, we need to answer some questions: What is the biochemistry of SCFAs, and how they are generated by gut microbiota? What are the bacteria producing of SCFAs and from which routes? How SCFAs are absorbed and transported in the gut by different mechanisms and receptors? How SCFAs involved in obesity and diabetes pathologies?