Substance and energy metabolism are the basis for all life activities and are largely regulated by cell-to-cell communication. Microbial cell-to-cell communication often occurs by releasing and receiving quorum sensing molecules (QSMs). QSMs are abundant and widely distributed in natural or artificial microbial communities, of which N-acyl homoserine lactones (AHLs), as a typical representative of QSMs, could strongly affect the physiological metabolism of microorganisms. Therefore, this review focuses on the role of AHL-mediated quorum sensing (AHL-QS) in the regulation of bacterial substance and energy metabolism. First, the typical molecular structures and general mechanism of the AHLs involved in this review were briefly introduced, and the findings regarding the regulatory mechanisms of AHLs in carbon metabolism (sugar uptake, Embden-Meyerhof-Parnas pathway, tricarboxylic acid cycle, hexose monophosphate pathway, amino acid and nucleotide metabolism and methane metabolism), nitrogen metabolism, sulfur metabolism and energy metabolism were discussed in detail. Finally, the regulation of AHL-QS in bacterial substance and energy metabolism was concluded, and the perspectives were highlighted. The progressive findings on the AHL-mediated QS involved in substance metabolism and energy metabolism are systematically and comprehensively summarized in this review. Thorough insight into the role of QS in metabolic processes is hopefully provided.