Alzheimer’s disease (AD) is the most common type of dementia affecting elderly people. This neuropathology is characterized by a highly complex and interconnected etiology including cholinergic deficit, amyloid deposits, neurofibrillary tangles and oxidative stress. The traditional mono-target approach is the only available therapy nowadays, but it is not efficient to stop this disease. Multi-targeted directed ligands (MTDLs) emerged in response to this problematic, being capable to interact with different causing factors simultaneously. During this PhD project, we have applied Ugi and Hantzsch multicomponent reactions for the synthesis of new multi-target adducts based on different antioxidant, anticholinergic, anti-monoamine oxidase, and calcium channel blockers scaffolds. These reactions provide access to a broad range of chemical diversity, which makes them suitable for a rapid synthesis of MTDLs hitting different targets related to the multifaceted etiology of Alzheimer’s disease.A total of 112 final compounds, spread over 8 series, have been synthesized, as cholinesterase and mono-amine oxidase inhibitors, antioxidants and calcium blockers. The biological evaluation has been assessed for the most of them, in order to confirm their activity as anti-AD agents. Such work demonstrated and validated the use of Ugi and Hantzsch reactions for the development of MTDLs as a potential treatment of AD.