Background The aim of our study was to investigate the changes in brain functional activity in heart transplant patients and to explore the relationship between abnormal spontaneous brain activity and cognitive function through amplitude of low-frequency fluctuations (ALFF). Methods Sixty-eight heart transplant patients and 56 healthy controls were assessed by the Montreal Cognitive Assessment (MoCA) scale and the Mini-Mental Status Examination (MMSE) scale, and resting-state functional magnetic resonance scans were performed. Cortical analysis was applied to calculate the ALFF, and two-sample t test was used to detect differences of mean ALFF in the brain region between the two groups. In addition, the correlations between abnormal functional activity brain regions, cognitive functions, and clinical indicators were analyzed. Results Heart transplant patients had significantly lower MoCA scores and MMSE scores compared to healthy subjects. ALFF were found to be decreased in the right cerebellum anterior lobe, left parahippocampal gyrus, left temporal lobe, left parietal lobe, and right postcentral gyrus, and increased in the right superior frontal gyrus and left middle frontal gyrus. In addition, ALFF in right superior frontal gyrus was positively correlated with MoCA score (r = 0.397, P < 0.05), MMSE score (r = 0.356, P < 0.05), stroke volume (SV, r = 0.412, P < 0.05), and left ventricular ejection fraction (LVEF, r = 0.614, P < 0.05) in heart transplant patients. Conclusions Cognitive function is impaired in heart transplant patients. The brain activity was altered in heart transplant recipients compared to healthy controls. ALFF changes in these brain regions may be associated with altered hemodynamics after transplantation, leading to impaired cognitive function. These findings help us to understand the neural mechanisms of cognitive changes in heart transplant recipients and provide a basis for developing interventions and rehabilitation strategies.