The mechanisms underlying the impact of metabolic syndrome on cognitive dysfunction in patients with schizophrenia remain unclear. The present study employed a two-factor factorial design to investigate the effects of metabolic syndrome on white matter microstructure in schizophrenia and its association with cognitive function. A total of 187 participants were included and classified into four groups based on the diagnoses of schizophrenia and metabolic syndrome: schizophrenia patients with metabolic syndrome (SZ-wMS), schizophrenia patients without metabolic syndrome, healthy controls with metabolic syndrome, and healthy controls without metabolic syndrome. Diffusion tensor imaging data were acquired. Using diffusion tensor model, fractional anisotropy (FA) was calculated to characterize the microstructural integrity of white matter. Peripheral metabolic indices and multiple domains of cognitive function were also assessed. The SZ-wMS group showed further reduced FA in the right sagittal stratum. Within the two-factor analytical framework, an interaction effect between metabolic syndrome and schizophrenia on FA in the right sagittal stratum was identified. Correlation analyses revealed that reduced FA in the right sagittal stratum was associated with impaired language function in patients with schizophrenia. Moreover, mediation analysis indicated that body mass index might indirectly affect language function by influencing FA in the right sagittal stratum. In summary, reduced integrity of white matter fibers in sagittal stratum may represent a potential neural mechanism underlying the comorbidity of schizophrenia and metabolic syndrome and may be associated with language dysfunction in schizophrenia.