Purpose Obstructive sleep apnea-hypopnea syndrome (OSAHS) may affect cerebrovascular reactivity (CVR), representing cerebrovascular endothelial function, through complex cerebral functional changes. This study aimed to evaluate the change of CVR after 1-month and 6-month mandibular advancement device (MAD) treatment of patients with carotid atherosclerosis (CAS) combined with OSAHS. Methods Patients with carotid atherosclerosis combined with OSAHS who voluntarily accepted Silensor-IL MAD therapy were prospectively enrolled. All patients underwent polysomnographic (PSG) examinations and CVR evaluation by breath-holding test using transcranial Doppler ultrasound at baseline (T0), 1 month (T1), and 6 months (T2) of MAD treatment. Results Of 46 patients (mean age 54.4 +/- 12.4 years, mean body mass index [BMI] 27.5 +/- 4.5 kg/m(2)), 41 patients (responsive group) responded to the 1-month and 6-month treatment of MAD, an effective treatment rate of 89%. The remaining 5 patients (non-responsive group) were younger (47.4 +/- 13.5 years) and had a higher BMI (35.8 +/- 1.8 kg/m(2)). The responsive group had an improvement of apnea-hypopnea index (AHI) (events/h) from 33.0 +/- 25.0 (T0) to 12.4 +/- 10.4 (T1) and 8.7 +/- 8.8 (T2), P < 0.001; minimum arterial oxygen saturation (minSpO(2)) (%) increased from 79.8 +/- 9.1 (T0) to 81.8 +/- 9.4 (T1) and 85.2 +/- 5.4 (T2), P < 0.01; longest apnea (LA) (s) decreased from 46.5 +/- 23.1 (T0) to 33.3 +/- 22.7 (T1) and 29.4 +/- 18.5 (T2), P < 0.001; T90 (%) decreased from 10.3 +/- 14.9 (T0) to 6.1 +/- 11.8 (T1) and 3.3 +/- 7.5 (T2), P < 0.05. Sleep architecture of these patients also improved significantly. The responsive group had a significant increase in left, right, and mean breath-holding index (BHI): left BHI(/s) from 0.52 +/- 0.42 (T0) to 0.94 +/- 0.56 (T1) and 1.04 +/- 0.64 (T2), P < 0.01; right BHI(/s) from 0.60 +/- 0.38 (T0) to 1.01 +/- 0.58 (T1) and 1.11 +/- 0.60 (T2), P < 0.01; mean BHI(/s) from 0.56 +/- 0.38 (T0) to 0.97 +/- 0.55 (T1) and 1.07 +/- 0.59 (T2), P < 0.01), suggesting improved CVR. Conclusion Effective MAD therapy is beneficial for restoring cerebrovascular endothelial function in patients with CAS and OSAHS in a short period (1 month and 6 months).