Objective: To evaluate the clinical efficacy of cranial electrotherapy stimulation (CES) as an adjuvant therapy for Alzheimer's disease (AD). Methods: A total of 120 AD patients were allocated into two groups according to different treatment methods, 60 cases in each group. The control group was treated with Donepezil treatment, and the observation group was treated with CES combined with Donepezil. The treatment course for both groups was 8 weeks. Assessments were conducted before and after treatment using a battery of standardized scales, including the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), and the Activities of Daily Living (ADL) scale, to evaluate cognitive function, behavioral and psychological symptoms, and daily living activities, respectively. Serum levels of β-amyloid 1-42 (Aβ1-42), phosphorylated tau protein (P-tau), and brain-derived neurotrophic factor (BDNF) were also measured and compared between the two groups. Results: The total effective rate in the observation group was higher than that in the control group (88.33% vs. 73.33%, P<0.05). Post-treatment, the scores on the ADAS-Cog and BEHAVE-AD scales, and serum levels of Aβ1-42 and P-tau in observation group were lower than those in the control group (P<0.05), and the scores on the MMSE, ADL scales, and BDNF levels were higher than those in the control group (P<0.05). Conclusion: Adjunctive use of CES in AD treatment can enhance cognitive function and improve overall clinical efficacy. The underlying mechanism may be associated with the modulation of serum Aβ1-42, P-tau, and BDNF levels.