Background: Curcumin possesses multifunctional pharmacological properties, including antioxidant, anti-inflammatory, and antidiabetic properties. We investigated whether curcumin can improve pathological changes associated with Alzheimer's disease (AD), including amyloid β (Aβ), protein kinase B (PKB, also termed Akt), and glycogen synthase kinase 3β (GSK3β) levels and expression. Materials and Methods: Alzheimer's transgenic APPSWE/PS1ΔE9 mice and wild-type mice were treated with curcumin by intragastric administration for 2 weeks at 2 and 5 months of age, respectively. Aβ plaques and contents in the brain and retina were measured by immunohistochemistry and enzyme-linked immune sorbent assay, respectively, while the expression of Akt and GSK3β was tested by RNA isolation and quantitative real-time polymerase chain reaction. Blood of patients with AD and age-matched healthy controls was used to determine the contents of Aβ, Akt, and GSK3β. Results: Curcumin treatment decreased Aβ accumulation in the early stages of AD at 5 months (P < 0.001). It also improved AD-associated pathological changes, including upregulation of Akt (P < 0.01) and downregulation of GSK3β (P < 0.01). In addition to AD-associated changes, the proinflammatory cytokine interleukin (IL)-1β was significantly decreased with curcumin treatment (P < 0.05). Conclusion: In the early stage of AD, curcumin can suppress Aβ accumulation, upregulate the expression of Akt, downregulate the expression of GSK3β, and inhibit the proinflammatory cytokine IL-1β. But in the late stage, curcumin has an insignificant inhibitory effect on GSK3β. In patients with AD, a low expression of Akt and a high expression of GSK3β were observed. Curcumin may have a similar effect on patients with AD by regulating these protein expressions and can be used to improve the pathological features of AD in the early stages of the disease.