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Myo‐inositol‐1‐phosphate synthase (MIPS) is a key rate limiting enzyme in myo‐inositol biosynthesis. The MIPS gene has been shown to improve tolerance to abiotic stresses in several plant species. However, its role in resistance to biotic stresses has not been reported. In this study, we found that expression of the sweet potato IbMIPS1 gene was induced by NaCl, polyethylene glycol (PEG), abscisic acid (ABA) and stem nematodes. Its overexpression significantly enhanced stem nematode resistance as well as salt and drought tolerance in transgenic sweet potato under field conditions. Transcriptome and real‐time quantitative PCR analyses showed that overexpression of IbMIPS1 up‐regulated the genes involved in inositol biosynthesis, phosphatidylinositol (PI) and ABA signalling pathways, stress responses, photosynthesis and ROS‐scavenging system under salt, drought and stem nematode stresses. Inositol, inositol‐1,4,5‐trisphosphate (IP₃), phosphatidic acid (PA), Ca²⁺, ABA, K⁺, proline and trehalose content was significantly increased, whereas malonaldehyde (MDA), Na⁺ and H₂O₂ content was significantly decreased in the transgenic plants under salt and drought stresses. After stem nematode infection, the significant increase of inositol, IP₃, PA, Ca²⁺, ABA, callose and lignin content and significant reduction of MDA content were found, and a rapid increase of H₂O₂ levels was observed, peaked at 1 to 2 days and thereafter declined in the transgenic plants. This study indicates that the IbMIPS1 gene has the potential to be used to improve the resistance to biotic and abiotic stresses in plants.