Moxibustion has a definite clinical effect in improving the cognitive condition in individuals with mild cognitive impairment (MCI), but its underlying neural mechanism remains elusive. This study aimed to investigate the alterations in spontaneous brain activity and cognitive function following moxibustion therapy in MCI patients. This study enrolled a cohort of 33 MCI subjects and 30 matched healthy controls (HCs). MCI subjects underwent a two-month regimen of moxibustion. Employing resting-state functional magnetic resonance imaging, we utilized regional homogeneity (ReHo) analysis to evaluate the changes in brain activity. Cognitive function was evaluated by using the Mini-Mental State Examination and Montreal Cognitive Assessment. There existed aberrant ReHo values in different brain areas mainly involved in the default mode network (DMN) in MCI subjects compared with HCs. After moxibustion treatment, MCI subjects showed an inverse in ReHo values from baseline in the hippocampus/parahippocampus and insula, as well as an increase inReHo value in the middle frontal gyrus. Notably, the ReHo alterations in the left hippocampus/parahippocampus and middle frontal gyrus were associated with cognitive improvement in MCI patients. Abnormal neural activity occurred in MCI subjects mainly within the DMN. Moxibustion therapy may facilitate cognitive improvement in MCI subjects by modulating brain activity, particularly by reversing the neural activity within the DMN and salience network. These results underscore the therapeutic potential of moxibustion as an early intervention strategy for Alzheimer's disease.