<p>Alzheimer's disease (AD) is marked by a gradual decline in cognitive abilities, primarily resulting from the degeneration of the cerebral cortex and hippocampus. This degeneration is closely associated with the abnormal buildup of amyloid beta (Aβ) plaques and hyperphosphorylated tau proteins, which initiate a chronic neuroinflammatory response arbitrated by the initiation of the brain's resident immune cells. The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is pivotal in regulating this inflammatory response. Chronic neuroinflammation results in the release of pro-inflammatory cytokines, such as interleukin-1β -1β (IL-1β), which disrupt neuronal function, hinder synaptic plasticity, and contribute to neuronal death. Additionally, neuroinflammation compromises the blood–brain barrier's (BBB) integrity, allowing peripheral immune cells to worsen the inflammatory response, leading to neurodegeneration and impaired neurogenesis, which further exacerbates cognitive deficits. Cellular stressors such as mitochondrial impairment, elevated reactive oxygen species (ROS), and lysosomal rupture initiate inflammasome activation, leading to the release of the pro-inflammatory cytokines IL-1β and interleukin-18 (IL-18). Current therapeutic approaches primarily focus on reducing Aβ levels, but their effectiveness on cognitive outcomes remains limited, highlighting the necessity for innovative strategies that target neuroinflammation. This review underscores the potential of various chemical scaffolds in developing novel treatments for AD. By building on these insights, preclinical research could further assess their safety, effectiveness, and ability to penetrate the BBB, along with optimal formulation strategies paving the way for clinical trials. This contributes to the growing field of inflammasome-targeted AD therapies, which may combine with existing treatments for synergistic effects, ultimately improving prognosis for the millions affected by AD.</p> Graphical abstract <p></p>