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Drought stress is one of the major constraints for soybean growth and productivity worldwide. The study was aimed to investigate drought-induced physiological and proteomic changes in soybeans, as well as drought relief using exogenous hydrogen peroxide (H
2
O
2
). In drought-stressed plants, H
2
O
2
spray on the leaf surface improved relative water content (RWC), net photosynthetic rate (Pn), and stomatal conductance (Gs). Furthermore, exogenous H
2
O
2
reduced drought stress-induced endogenous MDA and H
2
O
2
levels, as well as increased the key antioxidant enzymes (SOD,CAT, APX and POD) activity and proline content in H
2
O
2
-treated soybean plants. These findings showed that H
2
O
2
treatment significantly reduced drought stress by increasing the antioxidative defense system and osmotic adjustment. Furthermore, using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, a total of 27 differently expressed proteins was identified, wherein 23 were up-regulated and 4 were down-regulated under drought condition. These proteins were found to be involved in photosynthesis, energy and metabolism, plant defense and antioxidant, signaling and transport, and transcription regulation in response to H
2
O
2
treatment in soybean under drought stress, according to in silico interactome analysis. These findings add to our understanding of H
2
O
2
-mediated drought stress alleviation, as well as the physiological and molecular responses of soybean to drought stress.