Drought is among the most severe environmental stressors, imposing detrimental effects on plant growth and development. In this study, we have identified a class III peroxidase gene, OsPrx114, which was induced under PEG (Polyethylene glycol) and drought conditions and found to be localized in both the plasma membrane and endoplasmic reticulum. The promoter region of OsPrx114 encompasses cis-elements, including ABRE (ABA response elements), MBS (MYB binding elements), and W-box, which are likely contributors to drought tolerance. In comparison to Nipponbare (Nip) plants, the overexpression of OsPrx114 enhanced drought tolerance by reducing the accumulation of reactive oxygen species (ROS) through the upregulation of enzyme activities, such as peroxide dismutase (POD) and catalase (CAT). This was accompanied by an increase in proline (Pro) content and a decrease in malondialdehyde (MDA) content. Furthermore, a series of assays including yeast one-hybrid, electrophoretic mobility shift, and dual luciferase assays, demonstrated that the transcription factor OsWRKY50 binds to the W-box (TTGACC) within the promoter of OsPrx114, thereby activating its transcription. OsWRKY50 plays a positive role in regulating OsPrx114-mediated drought resistance by mitigating ROS accumulation in rice. These findings offer a molecular foundation for comprehending the function of the OsWRKY50-OsPrx114 module in response to drought stress in rice.