Objective To investigate the changes of thyroid hormone levels in the patients with Alzheimer’s disease (AD) and the clinical efficacy of huperzine A combined with memantine. Methods Eighty-six AD patients [48 males and 38 females, at an age of (69.9±8.6) years] admitted in our department from April 2014 to May 2016 were recruited in this study. Another 65 age-matched elders [33 males and 32 females, at an age of (67.7±9.3) years] who taking physical examination in our hospital during the same period served as controls. The AD patients were randomly divided into huperzine A group and oxiracetam group (n=43 for each group). Combination of memantine was given the patients of both groups. The serum levels of thyroid hormones were measured before and after the treatment. Mini-mental state examination (MMSE) and activities of daily living (ADL) scaling were used to evaluate their mental status and living abilities. Results Before the treatment, the AD patients had significantly lower serum levels of thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine (TT4), and free T3 (FT3) than the normal elders (P<0.05). After 6 months’ treatment, these levels were increased, the MMSE scores were elevated, and the scores of ADL were decreased in the huperzine A group. While except for the increment of TT4, other hormones had no obvious changes in the oxiracetam group, though the scores of MMSE were improved and the scores of ADL were decreased. Huperzine A treatment resulted in better outcomes in the serum levels of TSH and TT4 and scores of MMSE and TT4 when compared with oxiracetam treatment (P<0.05). Conclusion AD patients have significantly lower levels of thyroid hormones, and are at high risk for reduced thyroid function. Huperzine A combined with memantine shows good efficacy and improves thyroid hormone levels in the aged AD patients.