Background: Neuroimaging studies have shown that the high synchrony of spontaneous neural activity in the homotopic regions between hemispheres is an important functional structural feature of normal human brains, and this feature is abnormal in the patients with various mental disorders. However, little is known about this feature in obsessive-compulsive disorder (OCD). This study aimed to further analyze the underlying neural mechanisms of OCD and to explore whether clinical characteristics are correlated with the alerted homotopic connectivity in patients with OCD. Methods: Using voxel-mirrored homotopic connectivity (VMHC) during resting state, we compared 46 OCD patients and 46 healthy controls (HCs) matched for age, gender, and education level. A partial correlation analysis was used to investigate the relationship between altered VMHC and clinical characteristics in patients with OCD. Results: Patients with OCD showed lower VMHC than HCs in fusiform gyrus/inferior occipital gyrus, lingual gyrus, postcentral gyrus/precentral gyrus, putamen, and orbital frontal gyrus. A significant positive correlation was observed between altered VMHC in the angular gyrus/middle occipital gyrus and illness duration in patients. Conclusions: Interhemispheric functional imbalance may be an essential aspect of the pathophysiological mechanism of OCD, which is reflected not only in the cortico-striatothalamo-cortical (CSTC) loop but also elsewhere in the brain.