To study the effect of partially hydrolyzed guar gum (PHGG) on learning and memory ability of APP/PS1 Alzheimer's disease (AD) mice, PHGG dietary intervention was taken by APP/PS1 mice for 3 months, and the learning and memory ability was measured by Morris water maze and step-through passive avoidance tests. The morphological changes of brain tissue and the number of neurons were observed, and the expression of apoptosis-related proteins was determined by Western blotting. Furthermore, the expression levels of amyloid beta protein and phosphorylated Tau protein were detected by immunofluorescence. The result showed that compared with APP/PS1 model mice, PHGG significantly improved the reactivity, coarseness and lordokyphosis. The time and distance of entering the target quadrant, and the number of crossing platform by PHGG treatment were increased by 81.6%, 58.0% and 171.4% (P<0.05), respectively. Meanwhile, the number of neurons in the cerebral cortex and hippocampus was increased. The protein expression ratio of Bcl-2/Bax in whole brain tissue was increased by 54.9%, compared to APP/PS1 mice (P<0.05). The expressions of β-amyloid protein in cerebral cortex and hippocampus were decreased by 32.0% and 55.0% (P<0.05), and the expressions of phosphorylated Tau protein were decreased by 52.3% and 62.6% (P<0.01), respectively. Furthermore, PHGG treatment significantly reduced the expression of TLR4 (by 42.0%) and NF-κB (by 46.8%) proteins in whole brain tissue of APP/PS1 mice (P<0.05). PHGG could significantly improve the cognitive impairment of AD mice, and inhibit the cell apoptosis and neuronal damage in the cerebral cortex and hippocampus of brain tissue by regulating TLR4/NF-κB signaling pathway. The results provided a scientific basis for the development of PHGG as a functional food ingredient for anti-AD.