The object of the present invention is to provide a stable isotope enrichment device and a stable isotope enrichment method capable of reducing the discharge amount of toxic or combustible substances or substances causing environmental load in the atmosphere and reducing the amount of raw materials used. The present invention provides a stable isotope enrichment device, including: a distillation column group in which a plurality of distillation columns are connected in a cascade; a raw material supply line (30) that supplies a raw material into a first distillation column (1); a product line (31) that withdraws a product from another distillation column located on the secondary side of the first distillation column (1); an isotope-depleted fluid withdraw line (32) that withdraws an isotope-depleted gas or an isotope-depleted liquid from the first distillation column (1) or another distillation column located on the primary side of the one distillation column (1); an isotope exchange reactor (22) at which the isotope-depleted gas or the isotope-depleted liquid is subjected to an isotope exchange reaction, the isotope-depleted gas or the isotope-depleted liquid is regenerated such that the concentration of molecules containing a target stable isotope in the isotope-depleted gas or the isotope-depleted liquid approaches the natural abundance ratio, and an isotope-regenerated gas or an isotope-regenerated liquid is produced; and an isotope-regenerated fluid return line (33) that re-supplies the isotope-regenerated gas or the isotope-regenerated liquid into the first distillation column (1).