Abstract: This review provides a comprehensive analysis of the research progress concerning isotopic fractionation during the formation and decomposition of natural gas hydrates, focusing on three aspects: research methodologies, isotopic fractionation effects, and their energy-environmental significance. The study posits that the primary research methods for isotope fractionation effect in the formation/decomposition process of natural gas hydrates were mainly experimental simulation and natural observation. These methods reveal significant isotopic compositional differences in fluids at various depths within the hydrate system, which are closely associated with the isotopic fractionation effects occurring during hydrate formation/decomposition. The formation/decomposition process of hydrates involves the superposition of several physicochemical processes, including dissolution/desorption, phase transition, fluid transport within porous media, and oxidative consumption. The phase transition process is temperature-controlled and represents a thermodynamic fractionation effect, while the dissolution/desorption, fluid transport, and oxidative consumption processes are primarily governed by environmental factors such as the pore structure of the porous media, temperature, pressure, oxygen content, and are time-dependent, representing a kinetic fractionation effect. Currently, the isotopic fractionation effects during hydrate formation/decomposition have been preliminarily applied to hydrate exploration signs, gas source identification, hydrocarbon accumulation mechanism studies, and resource assessment. They also provide new perspectives for explaining the rise in atmospheric methane concentrations and the isotopic shifts towards lighter values, as well as the rapid negative isotopic excursions during global warming periods in geological history. However, existing research has mainly focused on the phenomenological observation and qualitative analysis of isotopic fractionation during hydrate formation/decomposition. In the future, numerical simulation and molecular dynamics simulation should be used to supplement the research methods of isotope fractionation effect of hydrate, and the characteristics, influencing factors, mechanism and quantitative characterization of isotope fractionation in the formation/decomposition process of gas hydrate should be systematically studied.