Neuroinflammation is a key pathological hallmark of Alzheimer's disease (AD), characterized by the activation of resident immune cells in the brain and the infiltration of peripheral immune cells. This inflammation facilitates the deposition of amyloid-beta (Aβ) plaques and the abnormal hyperphosphorylation of tau protein, leading to neuronal damage and cognitive decline. Exercise has been shown to improve brain function and protect against neuroinflammation, oxidative stress, and synaptic dysfunction in AD models. The neuroprotective effects of exercise are mediated by various molecular factors, such as brain-derived neurotrophic factor (BDNF), clusterin (CLU), and irisin, which can be activated by exercise mimetics. Recent studies have demonstrated the efficacy of exercise mimetics in alleviating neuroinflammation and AD, making them a promising alternative for patients unable to perform regular physical exercise. This review focuses on the current state of knowledge regarding exercise mimetics, including their efficacy, regulatory mechanisms, progress, challenges, limitations, and future guidance for their application in AD therapy. Exercise mimetics can activate molecular pathways similar to those activated by exercise, providing a potential therapeutic approach for AD by reducing neuroinflammation and managing AD pathology.Neuroinflammation is a key pathological hallmark of Alzheimer's disease (AD), characterized by the activation of resident immune cells in the brain and the infiltration of peripheral immune cells. This inflammation facilitates the deposition of amyloid-beta (Aβ) plaques and the abnormal hyperphosphorylation of tau protein, leading to neuronal damage and cognitive decline. Exercise has been shown to improve brain function and protect against neuroinflammation, oxidative stress, and synaptic dysfunction in AD models. The neuroprotective effects of exercise are mediated by various molecular factors, such as brain-derived neurotrophic factor (BDNF), clusterin (CLU), and irisin, which can be activated by exercise mimetics. Recent studies have demonstrated the efficacy of exercise mimetics in alleviating neuroinflammation and AD, making them a promising alternative for patients unable to perform regular physical exercise. This review focuses on the current state of knowledge regarding exercise mimetics, including their efficacy, regulatory mechanisms, progress, challenges, limitations, and future guidance for their application in AD therapy. Exercise mimetics can activate molecular pathways similar to those activated by exercise, providing a potential therapeutic approach for AD by reducing neuroinflammation and managing AD pathology.