Inhibitors play an important role in preventing and controlling coal spontaneous combustion (CSC). In this study, the inhibitory effects of antioxidant-reduced glutathione (G-SH) on CSC were examined. Thermogravimetric-differential scanning calorimetry (TG-DSC), cross-point temperature (CPT), and oxidation product tests were used to examine the effect of G-SH on the tendency of CSC and compare the discrepancy in the inhibition effect of G-SH and the halogen inhibitor. The changes in the free radical type, concentration, and surface functional groups in coal before and after the addition of G-SH were analyzed using electron spin resonance spectroscopy (ESR) and Fourier transform infrared spectroscopy (FT-IR). Six common active radical models were constructed, and the thermodynamic parameters of the reaction were calculated using density functional theory (DFT). The results revealed that G-SH inhibits the spontaneous combustion of coal. The inhibitory effect of G-SH was significantly stronger than that of the halogen salt inhibitors CaCl2 and MgCl2, and the higher the concentration of G-SH, the stronger is the inhibitory effect. The characteristic temperature points in the thermogravimetric experiment of coal samples with G-SH shifted to a higher temperature zone, and the CO concentration and oxygen consumption were lower than those of raw coal. After G-SH treatment, the type and relative concentration of free radicals in coal were lower than those in raw coal, the content of aliphatic hydrocarbon functional groups and oxygen-containing functional groups decreased, and the content of sulfur-containing functional groups increased. According to the calculation of Gibbs free energy and reaction enthalpy, G-SH can effectively neutralize the active free radicals in the process of coal oxidation, and the reaction activity with the free radicals in the process of coal oxidation is ·OOH > ·OH > ·CH3 > RO· > R· > ROO·. According to the experimental results, it is inferred that G-SH continuously supplies a large number of hydrogen donors (·H) for the reaction during the oxidation process and simultaneously neutralizes carbon free radicals and carbon oxygen free radicals, thereby reducing the concentration and reactivity of free radicals in the whole chain reaction process and blocking the occurrence of coal-oxygen composite reaction.