Updated project metadata. Straw return is crucial for the sustainable development of rice planting. To investigate the response of rice leaves to rice straw return, we analyzed the physiological index of rice leaves and measured differentially expressed protein (DEPs) and differentially expressed metabolites (DEMs) levels in rice leaves by the use of proteomics and metabolomics approaches. The results showed that, compared with no rice straw return, rice straw return significantly decreased the dry weight of rice plants and nonstructural carbohydrate contents and destroyed the chloroplast ultrastructure. In rice leaves under rice straw return, 329 DEPs were upregulated, 303 DEPs were downregulated, 44 DEMs were upregulated, and 71 DEMs were downregulated. These DEPs and DEMs were mainly involved in various molecular processes, including photosynthesis, carbon fixation in photosynthetic organisms, glycolysis, and the citric acid cycle. Rice straw return promoted the accumulation of osmotic adjustment substances, such as organic acids, amino acids, and other substances, and reduced the material supply and energy production of carbon metabolism, thus inhibiting the growth of rice.