Abstract: Objective To observe the effect of small dose ziprasidone combined with donepezil hydrochloride in the treatment of Alzheimer's disease and the effect on sugar and lipid metabolism in patients. Methods One hundred patients with Alzheimer's disease admitted to the Third People's Hospital of Fuyang District from January 2016 to January 2018 were randomly divided into two groups, 50 in each group. The low dose group were given 20 mg ziprasidone combined 10 mg donepezil hydrochloride, while the high dose group were given 40 mg ziprasidone combined 10mg Donepezil hydrochloride. The changes of score of behavioral pathological assessment scale for Alzheimer's disease (BEHAVE-AD), nursing distress, Wechsler Adult Intelligence Test and Clinical Memory Scale (WAIS), blood sugar and blood lipid were compared between the two groups. Results After treatment, the BEHAVE-AD, nursing distress degree of two groups were better than before treatment, but the lower dose group was more significant (all P<0.05). In WAIS of two groups after treatment, the scores of each factor in low-dose group were better than that of high dose group (all P<0.05). After treatment, the scores of clinical memory scale in low dose group were significantly better than those in high dose group, except for the association study of portrait characteristics (all P<0.05). Compared with before treatment, the blood sugar, TG and TC levels in low dose group were increased after treatment, but the effect were not obvious (all P>0.05), meanwhile those in high dose group were increased with significant difference (all P<0.05). Conclusion Administration of 20 mg of ziprasidone combined with 10 mg of donepezil hydrochloride is more effective in treating patients with Alzheimer's disease, and the effect of high dose on blood sugar and lipid metabolism were more obvious.