Chronic stress and high levels of glucocorticoids produce functional and structural changes in brain and especially in the hippocampus, an important limbic system structure that plays a key role in cognitive functions including learning and memory. Alzheimer's disease (AD) is a chronic neurodegenerative disease that usually starts slowly and worsens over time. Indeed, cognitive dysfunction, neuronal atrophy, and synaptic loss are associated with both AD and chronic stress. Recent preclinical and clinical studies have highlighted a possible link between chronic stress, cognitive decline and the development of AD. It is suggested that Tau protein is an essential mediator of the neurodegenerative effects of stress and glucocorticoids towards the development of AD pathology. Recent findings from animal and humans studies demonstrated that saffron and its main constitutive crocin are effective against chronic stress-induced cognitive dysfunction and oxidative stress and slowed cognitive decline in AD. The inhibitory actions on acetylcholinesterase activity, aggregation of beta-amyloid protein into amyloid plaques and tau protein into neurofibrillary tangles, and also the antioxidant, anti-inflammatory, and the promotion of synaptic plasticity effects are among the possible mechanisms to explain the neuroprotective effects of saffron. New evidences demonstrate that saffron and its main component crocin might be a promising target for cognition improvement in AD and stress-related disorders.