BackgroundMild Cognitive Impairment (MCI), as a high risk of Alzheimer’s disease (AD), represents a state of cognitive function between normal aging and dementia. Moxibustion may effectively delay the progression of AD, while there is a lack of studies on the treatments in MCI. This study aimed to evaluate the effect of moxibustion treatment revealed by the amplitude of low-frequency fluctuation (ALFF) in MCI.MethodWe enrolled 30 MCI patients and 30 matched healthy controls (HCs) in this study. We used ALFF to compare the difference between MCI and HCs at baseline and the regulation of spontaneous neural activity in MCI patients by moxibustion. The Mini-Mental State Examination and Montreal Cognitive Assessment scores were used to evaluate cognitive function.ResultsCompared with HCs, the ALFF values significantly decreased in the right temporal poles: middle temporal gyrus (TPOmid), right inferior temporal gyrus, left middle cingulate gyrus, and increased in the left hippocampus, left middle temporal gyrus, right lingual gyrus, and right middle occipital gyrus in MCI patients. After moxibustion treatment, the ALFF values notably increased in the left precuneus, left thalamus, right temporal poles: middle temporal gyrus, right middle frontal gyrus, right inferior temporal gyrus, right putamen, right hippocampus, and right fusiform gyrus, while decreased in the bilateral lingual gyrus in MCI patients. The Mini-Mental State Examination and Montreal Cognitive Assessment scores increased after moxibustion treatment, and the increase in Mini-Mental State Examination score was positively correlated with the increase of ALFF value in the right TPOmid, the right insula, and the left superior temporal gyrus.ConclusionMoxibustion treatment might improve the cognitive function of MCI patients by modulating the brain activities within the default mode network, visual network, and subcortical network with a trend of increased ALFF values and functional asymmetry of the hippocampus. These results indicate that moxibustion holds great potential in the treatment of MCI.