Oxidative stress plays a critical role in the pathophysiology of Alzheimer's disease (AD). Reactive oxygen species (ROS) generated by mitochondrial dysfunction, dysregulated electron transport chain, and other sources contribute to the formation of aggregated β-amyloid and neurofibrillary tangles, which further stimulate ROS production. Oxidative stress damages lipids, proteins, and DNA, leading to neuronal death and AD. It also induces apoptosis through the modulation of ERK1/2 and Nrf2 pathways, increased GSK-3β expression, and decreased PP2A activity. Oxidative stress exacerbates AD by interfering with signaling pathways such as RCAN1, CREB/ERK, Nrf2, PP2A, NFκB, and PI3K/Akt. TNF-α is involved in oxidative stress stimulation, which can be regulated by drugs like etanercept to increase antioxidants. Other drugs such as pramipexole, memantine, carvedilol, and melatonin activate CREB/RCAN1 and Nrf2 pathways. Epigallocatechin gallate and genistein target Nrf2 and CREB pathways, activating downstream pathways like ARE and Keap1 to alleviate oxidative stress. Donepezil and resveratrol reduce oxidative stress and activate the AMPK pathway along with PP2A activation, promoting tau dephosphorylation and neuronal survival. This study details the role of oxidative stress in AD, major signaling pathways involved, and drugs targeting these pathways, which may aid in therapeutic advances for AD. Alzheimer's disease is a rapidly progressing neurodegenerative disorder leading to cognitive decline. Major pathologies include amyloid plaque deposition, neurofibrillary tangle formation, oxidative stress, cholinergic insufficiency, platelet aggregation, excitotoxicity, and neuroinflammation. Currently, only a few FDA-approved drugs provide symptomatic relief, including acetylcholinesterase inhibitors and a NMDA receptor blocker. Recent studies propose anti-Aβ monoclonal antibodies as potential treatments. Oxidative stress is a crucial contributor to AD progression, caused by an imbalance in free radicals and antioxidants. It disrupts biomolecules including lipids, proteins, and nucleic acids, leading to brain cell destruction. Mitochondria are a major source of reactive oxygen species, and mitochondrial dysfunction leads to oxidative stress-induced AD. The brain is highly susceptible to oxidative stress due to factors such as high iron levels, polyunsaturated fatty acids, energy demand, and oxygen consumption. β-oligomers in the AD brain may also promote ROS generation, damaging neurons and affecting cognitive functions. ROS generated during dysregulated cellular respiration damages neuronal functions. Reduced ATP production contributes to oxidative stress.Oxidative stress plays a critical role in the pathophysiology of Alzheimer's disease (AD). Reactive oxygen species (ROS) generated by mitochondrial dysfunction, dysregulated electron transport chain, and other sources contribute to the formation of aggregated β-amyloid and neurofibrillary tangles, which further stimulate ROS production. Oxidative stress damages lipids, proteins, and DNA, leading to neuronal death and AD. It also induces apoptosis through the modulation of ERK1/2 and Nrf2 pathways, increased GSK-3β expression, and decreased PP2A activity. Oxidative stress exacerbates AD by interfering with signaling pathways such as RCAN1, CREB/ERK, Nrf2, PP2A, NFκB, and PI3K/Akt. TNF-α is involved in oxidative stress stimulation, which can be regulated by drugs like etanercept to increase antioxidants. Other drugs such as pramipexole, memantine, carvedilol, and melatonin activate CREB/RCAN1 and Nrf2 pathways. Epigallocatechin gallate and genistein target Nrf2 and CREB pathways, activating downstream pathways like ARE and Keap1 to alleviate oxidative stress. Donepezil and resveratrol reduce oxidative stress and activate the AMPK pathway along with PP2A activation, promoting tau dephosphorylation and neuronal survival. This study details the role of oxidative stress in AD, major signaling pathways involved, and drugs targeting these pathways, which may aid in therapeutic advances for AD. Alzheimer's disease is a rapidly progressing neurodegenerative disorder leading to cognitive decline. Major pathologies include amyloid plaque deposition, neurofibrillary tangle formation, oxidative stress, cholinergic insufficiency, platelet aggregation, excitotoxicity, and neuroinflammation. Currently, only a few FDA-approved drugs provide symptomatic relief, including acetylcholinesterase inhibitors and a NMDA receptor blocker. Recent studies propose anti-Aβ monoclonal antibodies as potential treatments. Oxidative stress is a crucial contributor to AD progression, caused by an imbalance in free radicals and antioxidants. It disrupts biomolecules including lipids, proteins, and nucleic acids, leading to brain cell destruction. Mitochondria are a major source of reactive oxygen species, and mitochondrial dysfunction leads to oxidative stress-induced AD. The brain is highly susceptible to oxidative stress due to factors such as high iron levels, polyunsaturated fatty acids, energy demand, and oxygen consumption. β-oligomers in the AD brain may also promote ROS generation, damaging neurons and affecting cognitive functions. ROS generated during dysregulated cellular respiration damages neuronal functions. Reduced ATP production contributes to oxidative stress.