Objective: To observe the effect of curcumin on the expression of synapse-related proteins PSD-95 and Shank1 in APP/PS1 double transgenic mice. Method: Three-month-old APP/PS1 dtg mice were randomly divided into the model group, the positive Rosiglitazone control group and curcumin high (400 mg·kg -1 ·d -1 ), medium (200 mg·kg -1 ·d -1 ) and low (100 mg·kg -1 ·d -1 ) dose groups, with non-genetically modified mice with the same background as the normal group. After the oral administration for three months, immunohistochemistry and Western blot were adopted for detection. Result: According to the behavioral detection, the treatment group and the model group showed differences in the place navigation test and the spatial probe test to varying degrees (P < 0.01 or P < 0.05). The expression of PSD-95 and Shank1-positive cells of hippocampus CA1 region significantly decreased in model mice compared with normal control group (P < 0.01); while the curcumin intervention group showed recovery to some extend. Western blot results showed that the strap of PSD-95 protein expression became significantly thinner and lighter in the model group compared with the normal control group (P < 0.01); while the curcumin intervention group showed notably thicker and darker straps of PSD-95 protein expression (P < 0.05). Conclusion: Curcumin can increase the expression of synapse-related proteins PSD95 and Shank1 in APP/PS1 double transgenic mice, improve structure and plasticity of synapse in APP/PS1 double transgenic mice and enhance their learning and memory abilities.