Single-atom catalysts (SACs) have emerged as promising materials in energy conversion and storage systems due to their maximal atom utilization, unique electronic structure, and high efficiency. Among them, main-group metal-based SACs (the s-block and p-block metals) are emerging extraordinary materials and have attracted particular interest in the past few years but are still confronted with several challenges. Initiating with a critical overview of the fundamentals and unique advantages associated with main-group metals, the review proceeds to highlight several types of main-group metal-based SACs. These include s-block metals such as Mg and Ca, and p-block metals such as In, Bi, Al, Ga, Sb, Se, and Sn. The applications of these SACs in diverse chemical energy conversion processes are thoroughly explored. Finally, to promote the future development of highly efficient main-group metal SACs, the critical challenges and prospects in this emerging field are proposed. This review presents a fresh impetus and solid platform for the rational design and synthesis of high-performance main-group metal SAC catalysts for chemical energy conversion fields.