Salinity in the form of abiotic stress adversely effects plant growth, development, and productivity. Various osmoprotectants are involved in regulating plant responses to salinity; however, the precise role of trehalose (Tre) in this process remains to be further elucidated. The present study investigated the regulatory role of Tre in alleviating salt-induced oxidative stress in hydroponically grown rice seedlings. Salt stress (150 and 250 mM NaCl) for 72 h resulted in toxicity symptoms such as stunted growth, severe yellowing, and leaf rolling, particularly at 250 mM NaCl. Histochemical observation of reactive oxygen species (ROS; O2 (∙-) and H2O2) indicated evident oxidative stress in salt-stressed seedlings. In these seedlings, the levels of lipoxygenase (LOX) activity, malondialdehyde (MDA), H2O2, and proline (Pro) increased significantly whereas total chlorophyll (Chl) and relative water content (RWC) decreased. Salt stress caused an imbalance in non-enzymatic antioxidants, i.e., ascorbic acid (AsA) content, AsA/DHA ratio, and GSH/GSSG ratio decreased but glutathione (GSH) content increased significantly. In contrast, Tre pretreatment (10 mM, 48 h) significantly addressed salt-induced toxicity symptoms and dramatically depressed LOX activity, ROS, MDA, and Pro accumulation whereas AsA, GSH, RWC, Chl contents, and redox status improved considerably. Salt stress stimulated the activities of SOD, GPX, APX, MDHAR, DHAR, and GR but decreased the activities of CAT and GST. However, Tre-pretreated salt-stressed seedlings counteracted SOD and MDHAR activities, elevated CAT and GST activities, further enhanced APX and DHAR activities, and maintained GPX and GR activities similar to the seedlings stressed with salt alone. In addition, Tre pretreatment enhanced the activities of methylglyoxal detoxifying enzymes (Gly I and Gly II) more efficiently in salt-stressed seedlings. Our results suggest a role for Tre in protecting against salt-induced oxidative damage attributed to reduced ROS accumulation, elevation of non-enzymatic antioxidants, and co-activation of the antioxidative and glyoxalase systems.