Abstract: The use of eco-friendly insulation gases to replace SF₆ in various high-voltage electric apparatus is urgently desired in order to reach the emission peak and carbon neutrality. This review covers the challenges and state-of-the-art progresses on the studies of the green replacement gases. From the theoretical point of view, various structure-activity relationship models for dielectric strength, liquefaction temperature, global warming potential, safety measures (toxicity and flammability), and arc interruption have been clarified in detail. The relevant merits and defects are pointed out to make progress accordingly. The major defects of the theoretical models available to date include their strong dependence on the experimental training sets and the elusive physical picture for the descriptors. It is suggested to carry out systematic investigations on the multi-type dielectric gases and the mechanistic studies of the microscopic chemistry relevant to discharge, liquefaction, green-house effect, toxicity, flammability, and arc interruptions. It is demonstrated that the multi-dimensional structure-activity relationship models play an important role in high-through virtual screening and rational molecular design even though with many restrictions. The correlation between different dimensions is unclear yet and thus no new gases superior to SF₆ at all required aspects have been found up to date. On the basis of the chemical bond hybrid and group-substitution molecular design, two technical protocols are proposed for the development and innovation of the environmentally sustainable insulation gases for the sake of complete transition to SF₆-free technologies as fast as possible.