Alzheimer's disease (AD) is a progressive neurodegenerative disorder without a cure, with most cases being sporadic and age being the primary risk factor. The loss of synapses is closely linked to cognitive decline in AD patients and is considered an early mechanism preceding neuronal loss. Oxidative stress, caused by increased reactive oxygen species (ROS) due to mitochondrial dysfunction, metal imbalance, and reduced antioxidant defenses, affects synaptic activity and neurotransmission, leading to cognitive dysfunction. ROS also damage DNA, lipids, proteins, and disrupt calcium homeostasis, mitochondrial dynamics, and cellular architecture. Abnormal metabolism can increase amyloid-β (Aβ) and hyperphosphorylated tau, exacerbating mitochondrial dysfunction and ROS production, creating a vicious cycle. Despite evidence linking ROS to AD, antioxidant therapies have not consistently improved outcomes. This review discusses the role of oxidative stress in synaptic dysfunction, innovative therapeutic strategies, and the dual role of ROS in health and disease. AD is characterized by amyloid plaques, neurofibrillary tangles, and synaptic loss. Oxidative stress contributes to AD through mitochondrial dysfunction, metal imbalance, and ROS production. Mitochondrial ROS can damage the mitochondrial membrane, increasing ROS production and leading to synaptic dysfunction. ROS also contribute to Aβ and tau aggregation, which are essential for AD pathology. Antioxidant therapies have shown limited success, and while some compounds show promise, clinical trials have yielded inconclusive results. Non-pharmacological interventions like exercise and caloric restriction have shown positive effects on cognitive function and may be beneficial for AD prevention and treatment. Understanding the complex molecular mechanisms of AD is crucial for developing effective therapeutic strategies targeting oxidative stress and mitochondrial dysfunction.Alzheimer's disease (AD) is a progressive neurodegenerative disorder without a cure, with most cases being sporadic and age being the primary risk factor. The loss of synapses is closely linked to cognitive decline in AD patients and is considered an early mechanism preceding neuronal loss. Oxidative stress, caused by increased reactive oxygen species (ROS) due to mitochondrial dysfunction, metal imbalance, and reduced antioxidant defenses, affects synaptic activity and neurotransmission, leading to cognitive dysfunction. ROS also damage DNA, lipids, proteins, and disrupt calcium homeostasis, mitochondrial dynamics, and cellular architecture. Abnormal metabolism can increase amyloid-β (Aβ) and hyperphosphorylated tau, exacerbating mitochondrial dysfunction and ROS production, creating a vicious cycle. Despite evidence linking ROS to AD, antioxidant therapies have not consistently improved outcomes. This review discusses the role of oxidative stress in synaptic dysfunction, innovative therapeutic strategies, and the dual role of ROS in health and disease. AD is characterized by amyloid plaques, neurofibrillary tangles, and synaptic loss. Oxidative stress contributes to AD through mitochondrial dysfunction, metal imbalance, and ROS production. Mitochondrial ROS can damage the mitochondrial membrane, increasing ROS production and leading to synaptic dysfunction. ROS also contribute to Aβ and tau aggregation, which are essential for AD pathology. Antioxidant therapies have shown limited success, and while some compounds show promise, clinical trials have yielded inconclusive results. Non-pharmacological interventions like exercise and caloric restriction have shown positive effects on cognitive function and may be beneficial for AD prevention and treatment. Understanding the complex molecular mechanisms of AD is crucial for developing effective therapeutic strategies targeting oxidative stress and mitochondrial dysfunction.