Drought represents a prevalent abiotic stress in terrestrial plants, frequently impairing crop growth and yield. In this paper, we characterized the functional role of OsNAC25, a member of the NAC transcription factor family, in drought tolerance. OsNAC25 was predominantly localized in both the cytoplasm and nucleus, with its expression being markedly induced under drought conditions. Under severe drought stress, the overexpression of OsNAC25 rice exhibited decreased malondialdehyde (MDA) levels, attenuated oxidative damage, and improved survival rate during the vegetative growth stage. The transcriptome analysis revealed that OsNAC25 coordinates drought response through key pathways associated with phenylpropanoid biosynthesis, plant hormone signal transduction, and diterpenoid biosynthesis. Collectively, our findings highlight OsNAC25 as a pivotal transcriptional regulator governing drought resistance in rice. This study not only provides a candidate gene for improving drought tolerance in rice but also offers valuable insights into the molecular mechanisms underlying drought adaptation in cereal crops.