Organ ischemia reperfusion injury (IRI) is unavoidable in kidney transplantation and induces reactive oxygen species and causes organ damage. Although the effectiveness of molecular hydrogen for IRI has been reported, oral ingestion of hydrogen rich water and inhalation of hydrogen gas are still not widely used in clinical settings because of the lack of efficiency or difficulty in handling. We succeeded in generating a large amount of hydrogen molecules by crushing silicon (Si) to nano-sized particles and reacting with water. We orally administered the nano-sized silicon particles or relatively large-sized silicon particles to renal IRI rats. Rats were divided into four groups: sham-operated, IRI, IRI + nano Si, and IRI + large Si group. We observed that serum creatinine and urine protein significantly decreased 72 hours following IRI in rats that were administered nano Si particles. Serum malondialdehyde and urinary 8-hydroxydeoxyguanosine, which are oxidative stress markers, were also significantly decreased with the nano Si treatment. Transcriptome and gene ontology enrichment analysis showed that the oral intake of nano Si downregulated the biological processes related to oxidative stress, such as immune response, cytokine production, and extrinsic apoptotic signaling. Regulation of some genes in these pathways was validated by quantitative polymerase chain reaction. Furthermore, immunohistochemistry staining demonstrated that the nano Si treatment alleviated the interstitial macrophage infiltration and the tubular apoptosis, suggesting anti-inflammatory and anti-apoptotic effects. In conclusion, renal IRI was attenuated by oral administration of the nano-sized silicon particles, which is a novel hydrogen administration method.