The multifactorial pathogenic causes of Alzheimer's disease (AD), a progressive neurodegenerative illness marked by cognitive decline and memory impairment, include tau hyperphosphorylation, beta-amyloid accumulation, oxidative stress, neuroinflammation, and cholinergic deficiency. Current therapies do not stop the course of the disease; they simply relieve its symptoms. Recent developments in the synthesis and design of multi-target-directed ligands (MTDLs), which seek to concurrently alter several AD-related pathways, are highlighted in this review. The focus is on hybrid compounds that combine anti-amyloid properties, metal chelation, antioxidant action, and acetylcholinesterase inhibition. Promising pharmacological profiles and neuroprotective potential are demonstrated by pyrimidine derivatives and coumarin-lipoic acid conjugates produced via nanoparticle catalysis. Furthermore, kinase inhibitors that target DYRK1A and associated enzymes provide fresh opportunities to modify tau pathogenesis. The development of successful disease-modifying treatments for AD is made possible by the combination of innovative synthetic processes, logical drug design, and thorough biological assessment. There is potential for bettering treatment results and tackling the intricate etiology of Alzheimer's disease with further study in this area.