Europium-doped Gd2O3 nanotubes (Gd2O3:Eu3+ NTs) have been extensively applied in the field of bioscience for their photostability and magnetic properties. Nevertheless, the distribution and interaction between Gd2O3:Eu3+ NTs and metabolism of bone are not yet sufficiently understood. In this study, a systematic study of the toxicity and distribution of Gd2O3:Eu3+ NTs in mice after oral administration was carried out. The results showed that a small number of the Gd2O3:Eu3+ NTs could pass through biological barriers into the lung, liver, and spleen, but a high concentration was observed in bone. Furthermore, the effects of Gd2O3:Eu3+ NTs on bone metabolism were systematically studied in vitro and in vivo when accumulating in bone. After being administered to mice, the Gd2O3:Eu3+ NTs extremely enhanced the bone mineral density and bone biomechanics. In vitro the Gd2O3:Eu3+ NTs increased the alkaline phosphatase (ALP) activity and mineralization and promoted the expression of osteogenesis genes in preosteoblasts MC3T3-E1 through activation of the BMP signaling pathway. This study will be significant for appropriate application of Gd2O3:Eu3+ NTs in the biomedical field and expounding the molecular mechanism of bone metabolism.