Background: Evidence of dual sensory impairment (DSI) characterized by comorbid hearing impairment (HI) and visual impairment (VI) is limited in neuropsychiatric disorders. Moreover, the underlying mechanisms remain elusive. Methods: Using data from 169,165 UK Biobank participants, we compared cognition and mental health across the no sensory impairment, HI, VI, and DSI groups and investigated the association between the number of sensory impairments and neuropsychiatric disorders in longitudinal COX analyses. We also analyzed the associations of sensory function and its interaction with brain structure, functional connectivity, inflammatory markers, and metabolites and explored their mediating roles. Results: DSI participants exhibited poor cognition and mental health, and had a higher risk of neuropsychiatric disorders compared to those with HI/VI alone. Both HI and VI were linked to atrophic changes in the hippocampus, thalamus, precuneus, parietal cortex, middle temporal gyrus, etc., and reduced white matter integrity. Brain regions associated with HI and VI exhibited decreased functional connectivity with other cortexes. Hearing and visual performance exhibit a significant interaction in relation to cognitive function, mental health, and metabolites. Brain structures, inflammation, and metabolic biomarkers significantly associated with HI and VI mediated the relationship between sensory impairments and cognition/mental health. Conclusion: Compared to HI/VI alone, DSI is associated with poorer cognitive function, mental health, and a higher risk of neuropsychiatric disorders, potentially driven by the interaction between HI and VI. Additionally, HI and VI are linked to brain atrophy, reduced white matter integrity, and altered functional connectivity. Furthermore, brain structure, inflammation, and metabolic biomarkers mediate the relationship between sensory impairments and cognition/mental health.