Domain of Unknown Function 740 (DUF740) is a gene family that has not been functionally elucidated in rice, until now. We investigated the function of rice DUF740 gene family member, LOC_Os04g59420 ( OsSRDP- O ryza s ativa Stress Responsive DUF740 Protein) which showed upregulation in response to drought stress in the available global expression data. Transgenic plants of OsSRDP gene, driven by a stress-inducible promoter AtRd29A, were developed in the background of a drought stress sensitive rice cv. Pusa Sugandh 2 (PS2) and their transgene integration and copy number were confirmed by molecular analysis. Homozygous transformants showed better resilience than PS2 when subjected to drought, salinity and cold stresses but not heat stress. Transgenic plants maintained higher RWC, photosynthetic pigments and proline accumulation under drought and salinity stresses. Further, they exhibited less accumulation of reactive oxygen species (ROS) than PS2 under drought stress as seen from the transcript abundance studies of the ROS genes. Under cold stress, OsSRDP transgenic lines illustrated minimal cell membrane injury than PS2. Additionally, the transgenic plants showed resistance to virulent strain of rice blast fungus Magnaporthe oryzae. Altogether, our findings established that stress-inducible expression of OsSRDP can significantly enhance tolerance to multiple abiotic stresses and a biotic stress.