The Shuiyindong Gold Mine hosts one of the largest and highest-grade, strata-bound Carlin-type gold deposits discovered to date in Southwestern China. The outcrop stratigraphy and drill core data of the deposit reveal Middle–Upper Permian and Lower Triassic formations. The ore is mainly hosted in Upper Permian bioclastic limestone near the axis of an anticline. The gold is mainly hosted in arsenian pyrite and arsenopyrite, mainly existing in the form of crystal lattice gold, submicroscopic particles and nanoparticles. Fluorite commonly occurs at the vicinity of an unconformity between the Middle–Upper Permian formations, which is proposed to be the structural conduit that fed the ore fluids. Calcite commonly fills fractures at the periphery of decarbonated rocks, which contain high grade orebodies. This study aimed to verify the occurrence of two distinct hydrothermal events at the Shuiyindong, based on Sm–Nd isotope dating of the fluorite and calcite. For this purpose, rare-earth element (REE) concentrations, Sm/Nd isotope ratios, and Sm–Nd isochron ages of the fluorite and calcite were determined. The fluorite and calcite contain relatively high total concentrations of REE (12.3–25.6 µg/g and 5.71–31.7 µg/g, respectively), exhibit variable Sm/Nd ratios (0.52–1.03 and 0.57–1.71, respectively), and yield Sm–Nd isochron ages of 200.1 ± 8.6 Ma and 150.2 ± 2.2 Ma, with slightly different initial εNd(t) values of −4.4 and −1.1, respectively. These two groups of Sm–Nd isochron ages suggest two episodes of hydrothermal events at the Shuiyindong gold deposit. The age of the calcite probably represents the late stage of the gold mineralization period. The initial εNd(t) values of the fluorite and calcite indicate that the Nd was probably derived from mixtures of basaltic volcanic tuff and bioclastic limestone from the Permian formations.