Alzheimer’s disease (AD) is the most predominant neurodegenerative disorder and form of dementia around the globe. Despite its prevalence, only a few drugs approved for AD and all concerned with the symptoms rather than the underlying cause of the disorder. Classic neuropathological disease hallmarks (β-amyloid & NFT) and sporadic AD risk genes APOE that activate NF-κB, yet may incite pathology. NF-κB inhibition is a current strategy to counter neuroinflammation and neurodegeneration in the brain of individuals with AD, and numbers of NF-κB modulators are being examined in clinical trials. Modification of the NF-κB system focuses mainly on preventing oxidative stress with the pathway to cell death and managing the levels of neurotransmitters. This review summarizes several shreds of evidence indicating the upregulation of NF-κB in AD and illustrates its function in current efforts for a therapeutic approach. The goal of innovative research strategies is to modulate NF-κB, providing an alternate treatment that may help individuals with AD and generate hope for potential clinical advancements in AD.