Waterlogging stress (WLS), intensified by climate change, poses a significant threat to plant growth and productivity. While general plant tolerance mechanisms to WLS have been explored, sexual specific molecular responses in dioecious trees, such as mulberry ( Morus alba L.), remain poorly understood. This study integrated proteomic and transcriptomic analyses to investigate the responses of male and female mulberry plants under WLS. The results revealed that male plants showed a higher number of differentially expressed proteins (DEPs) associated with photosynthesis and metabolic resilience. In contrast, female responses to WLS shared substantial overlap with baseline sex-based proteomic features under control (CK) conditions, suggesting more stable metabolic regulation. Both plants exhibited a higher proportion of DEPs (46%) in the chloroplast, indicating a photosynthesis-related response. Transcriptomic data showed that under CK, females had 1,301 upregulated and 675 downregulated genes compared to males, indicating innate transcriptional divergence. When comparing male plants under WLS, we found 678 differentially expressed genes (DEGs) were downregulated, suggesting suppression of stress-responsive pathways. Under WLS, females activate more stress-responsive genes, with an enriched pathway in ion transport, carbohydrate and amino acid metabolism, and signal transduction. Conversely, males showed a weaker transcriptional response and suppression of key metabolic pathways. Notably, the transcript-protein correlation was stronger in females than in males, reflecting more coordinated molecular regulation in females under stress. Ultrastructural observations showed distinct subcellular damage between sexes: females exhibited vacuolar and chloroplast disintegration with a visible nucleus, whereas males displayed chloroplast swelling, plastid proliferation, and a slightly distorted, less-defined nuclear structure. These findings highlight sexual specific molecular and cellular strategies in mulberry under WLS, underscoring the importance of integrating multi-omics approaches to understand stress adaptation in dioecious species.