Objective: To investigate the effects of gastrodin, astragaloside and paeoniflorin from three types of traditional Chinese herbs against on β-amyloid plaques and memory ability in 5XFAD Alzheimer's disease (AD) transgenic mice. Methods: Seventy 5XFAD mice were randomly divided into seven groups, namely gastrodin-high and gastrodin-low dose groups (GAS-H, GAS-L), astragaloside-high and astragaloside-low dose groups (AST-H, AST-L), and paeoniflorin-high and paeoniflorin-low dose groups (PAE-H, PAE-L), and positive control group. Negative control groups were also established. After being treated for four months, 5XFAD mice were evaluated for memory ability and Aβ plaques, and the mechanism were was explored by utilizing cell model (over-expression Aβ and β-secretase). Results: Gastrodin, astragaloside and paeoniflorin enhanced the learning and memory ability of 5XFAD mice, and reduced Aβ in the cerebral homogenate and Aβ plaques in brain. Compared with the untreated transgenic positive group, Aβ plaques was reduced in hippocampus and cortex in the GAS-H group by 70.1% and 81.0%, in the AST-H group by 62.4% and 69.6%, and in the PAE-H group by 57.6% and 66.6% (P<0.01), respectively. Aβ was reduced in the cerebral homogenate of all groups. The effects were dose-dependent. In vitro study suggested a dose-dependent effect of gastrodin, astragaloside and paeoniflorin in reducing Aβ in cell models. Gastrodin suppressed BACE mRNA level by 32.9% (P<0.01), and suppressed β-secretase protein level by 47.9% (P<0.01). Conclusions: Three types of Chinese herbs can inhibit β-amyloid plaques in brain of AD. Gastrodin reduced Aβ production and accumulation by inhibiting β-secretase. Astragaloside and paeoniflorin have no demonstrable effects against β-secretase.