The protective effect of probiotics Bifidobacterium longum, B. animalis and their combination on age-related cognitive decline is studied in the present work. We developed D-galactose (gal) (150 mg/kg/d)-treated mice, and oral administration of B. longum, B. animalis and their combination for 12 weeks. The results showed that these probiotics revered D-gal-induced anxiety-like behaviour, uncoordinated movement, cognitive decline, and hippocampus senescence. These probiotics also reduced the hippocampal mRNA expressions of interleukin (IL)-1 beta, IL-6, tumour necrosis factor (TNF)-alpha, malondialdehyde (MDA) activity, and increased the activities of glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD). Additionally, the activation of toll-like receptor 4 (TLR4), nuclear-factor-kappa B (NF-kappa B) and downregulation of sirtuin 1 (Sirt 1) proteins was restored by probiotics treatment. Based on the results, we concluded that B. longum, B. animalis and their combination might ameliorate age-related cognitive deficits in D-gal-treated mice, potentially by inhibiting NF-kappa B/TLR4 induced-neuroinflammation and oxidative stress through up-regulating the expression of Sirt 1.