To explore the effects of traditional Chinese medicine (TCM) treatment based on syndrome differentiation on the cognitive function of patients with severe Alzheimer’s disease (AD). Methods: Fifty patients with severe AD were selected and randomly divided into the Chinese medicine (CM) group and western medicine (WM) group with 25 patients in each group. Patients in the CM group were treated once every 4 weeks by TCM treatment based on syndrome differentiation: the patients of heart-qi deficiency were treated with“Tiaoxin Recipe”and of kidney-essence deficiency with“Bushen Recipe”, and patients with phlegm and blood stasis were additionally given“Mengshi Guntan Pellet”and“Xuefu Zhuyu Capsule”respectively. Patients in the WM group were treated with donepezil hydrochloride. The therapeutic course was 48 weeks. The scores of the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Fuld Object-Memory Evaluation (FOM), Rapid Verbal Retrieve (RVR), and Block Design (BD) before and after treatment were observed and compared. Results: In both groups, there was no statistical difference in MMSE, FOM numerator, FOM denominator, RVR, and BD scores before and after treatment (P>0.05). However, CDR scores in the CM group decreased after 24 and 48 weeks of treatment (P<0.05, P<0.01), and CDR scores in the WM group decreased after 48 weeks of treatment (P<0.05). Conclusion: The cognitive function of patients with severe AD did not deteriorate after TCM treatment based on syndrome differentiation, and to some extent, the disease severity was reduced.