Objective To investigate the effect of cyaniding-3-glucoside (Cy3G) on glucose and lipid metabolism in the APP^swe/PS1^ΔE9 mouse model of Alzheimer's disease (AD). Methods Seven-month-old APP^swe/PS1^ΔE9 (PAP) mice were randomly divided into model group (PAP), Cy3G treatment group (PAPCy, 5 mg/kg/d) and negative-control group (nPAP). In addition, age-matched and normal wild-type of C57BL/6J mice were selected and divided into vehicle group (WT), Cy3G intervention group (WTCy, 5 mg/kg/d). Each group containing 12 mice, with equal number of male and female mice. After 8-week Cy3G supplementation, microPET/CT was used to measure cerebral glucose metabolism rate of mice in each group. Biochemical methods were used to detect the liver/kidney function as well as indicators associated with lipid metabolism. After weighting brain tissue, the brain coefficient was tested and pathological examination was used to observe tissues changes. Transmission electron microscope was used to observe neuropathological amyloid plaques deposition. Western-blot was used to determine protein levels of AKT and JNK. Results Compared with the WT group, PAP mice had low levels of ¹⁸F-FDG uptake rates, especially in the regions of the frontal lobe and hippocampus accompanied by the decreased brain coefficient and amyloid plaques deposition in hippocampus. And levels of aspartate transaminase (AST) and lactic dehydrogenase (LDH) were also increased in PAP mice, but lipid metabolism index was relatively normal. In addition, the expression of JNK was decreased and AKT was increased in mice of PAP. However, in the PAPCy group, ¹⁸F-FDG uptake rates were obviously increased in the regions of the frontal lobe and hippocampus compared with those in the PAP mice. And the reduction of brain atrophy and amyloid plaques deposition, normal lipid metabolism and no obvious liver/kidney toxicity were also observed. Cy3G also could reverse the changes of JNK and AKT protein. Conclusions Cy3G can improve glucose metabolism disorders instead of lipid metabolism, inhibit the senile plaques deposition in hippocampus and regulate insulin resistance and inflammatory reaction associated with JNK/AKT pathway. Thus, Cy3G has a good safety profile and may be used as an ideal alternative to traditional disease-modifying treatments against AD.