As efficient and sustainable proteins, single-cell proteins (SCPs) demonstrate significant potential in alleviating the constraints of traditional agricultural resources and reducing the carbon footprint of food manufacturing. Low-carbon C1/C2 feedstocks, such as carbon dioxide, methanol, and acetate, offer distinct advantages, including broad availability, low costs, and minimal carbon footprints. However, the assimilation of these feedstocks and the accumulation of proteins are still limited by key bottlenecks such as poor host cell adaptability, imbalanced metabolic flux distribution, and inefficient energy supply. In recent years, remarkable progress has been achieved in the discovery, evaluation, and rational engineering of host strains for the efficient bioconversion of C1/C2 feedstocks. The application of synthetic biology, metabolic engineering, and laboratory adaptive evolution has enabled the continuous improvements of the strain tolerance to C1/C2 feedstocks, assimilation efficiency, and intracellular protein accumulation capacity. On the basis of these advancements, various SCP production processes utilizing C1/C2 feedstocks are gradually advancing toward pilot-scale and industrial applications. This review systematically summarizes the strategies for constructing chassis cells that efficiently utilize C1/C2 feedstocks, key metabolic engineering technologies driving efficient SCP production, and the current technological and industrial status of SCP production from different C1/C2 feedstocks. Furthermore, it discusses challenges related to energy efficiency, nutritional quality, safety, and downstream scale-up, aiming to provide a theoretical foundation and technical reference for the sustainable development and industrial application of SCPs produced from C1/C2 feedstocks.