To determine whether berberine could improve depression and anxiety in 5XFAD Alzheimer’s disease (AD) model mice. Methods: A total of 48 3-month-old 5XFAD transgenic AD model mice were randomly allocated into 4 groups with 12 mice in each: control group, low-dose berberine group (50 mg/kg), medium-dose berberine group (100 mg/kg), and high-dose berberine group (150 mg/kg). Mice were given intragastric administrations of berberine every day for 90 days. The changes in behavior indicators of the 5XFAD mice were observed by the open field test, elevated plus maze test, tail suspension test, and forced swimming test. Results: Compared with the control group, the low-dose berberine group showed decreased forced swimming time, decreased tail suspension time, increased time spent in open arms of the elevated plus maze, and increased total distance traveled in the elevated plus maze (P<0.05); the medium-dose berberine group showed decreased forced swimming time, decreased tail suspension time, increased time spent in open arms of the elevated plus maze, increased open arm entries in the elevated plus maze, increased total distance traveled in the elevated plus maze, increased time spent in the central area of the open field, and increased distance traveled in the central area of the open field (P<0.01); the high-dose berberine group showed decreased forced swimming time, decreased tail suspension time, increased time spent in open arms of the elevated plus maze, increased open arm entries in the elevated plus maze, and increased time spent in the central area of the open field (P<0.05). Moreover, the effect of medium-dose berberine was the most apparent. Conclusion: Berberine could improve depression and anxiety in 5XFAD mice.