The garnet structure Y3Fe5O12 (YIG) possesses a high immobilization capacity for actinides. However, the related research on the sensitivity of garnet structures to irradiation damage is still in its infancy. Herein, we synthesize Y3-xNdxFe5O12 (x = 0.1, 1.8) ceramics and irradiate them with 2 MeV α-particle irradiation to fluences ranging from 1 × 1014 to 1 × 1017 ions/cm2 at room temperature. We evaluated the effects of irradiation damage on the phase transition and chemical stability. An amorphous layer with a thickness of 84 nm is formed by irradiation, though the grain shape and element distribution remain uniform after irradiation. In addition, Y3-xNdxFe5O12 (x = 0.1, 1.8) ceramics exhibit excellent chemical stability (∼ 10−5 g m−2 · d−1) in the leaching process. Restricted by the topological structure of garnet, the increase in solid solubility does not lead to a change in the radiation tolerance of the garnet structure, which means that garnet of different compositions should have similar and predictable radiation tolerance.