The article reviews the potential of cinnamic acid derivatives as multi-target-directed ligands (MTDLs) for the treatment of Alzheimer's disease (AD). AD is a neurodegenerative disorder characterized by progressive cognitive decline, with no definitive cure or effective long-term treatment. Current therapies primarily focus on acetylcholinesterase (AChE) inhibition, which provides temporary relief. Promising alternatives include butyrylcholinesterase (BuChE) inhibitors, MTDLs targeting multiple AD factors, and compounds that address oxidative stress and inflammation. Cinnamic acid derivatives, known for their neuroprotective properties, show enhanced efficacy when combined with established AD agents. The review highlights the adaptability and combinability of cinnamic acid as a basic structure, with methoxy substitutions at the para-position and electron-withdrawing groups showing increased efficacy. The molecular volume effect is also noted as worthy of further investigation. The article discusses the synthesis and evaluation of various cinnamic acid derivatives, including tacrine derivatives, isoquinoline and quinoline derivatives, benzylpiperidine derivatives, β-carbolines analogs, tryptamine derivatives, and rivastigmine derivatives. These compounds exhibit multifunctional activities, including AChE and BuChE inhibition, Aβ accumulation inhibition, antioxidant properties, and neuroprotective effects. The methoxy substitution at the para-position of cinnamic acid significantly enhances potency, while electron-withdrawing groups generally increase activity. The selectivity of the enzymes depends on the molecular volume, suggesting further investigation into this aspect. Overall, the review underscores the need for extensive research into cinnamic acid hybrids for the prevention and treatment of AD, given their promising multifunctional properties.The article reviews the potential of cinnamic acid derivatives as multi-target-directed ligands (MTDLs) for the treatment of Alzheimer's disease (AD). AD is a neurodegenerative disorder characterized by progressive cognitive decline, with no definitive cure or effective long-term treatment. Current therapies primarily focus on acetylcholinesterase (AChE) inhibition, which provides temporary relief. Promising alternatives include butyrylcholinesterase (BuChE) inhibitors, MTDLs targeting multiple AD factors, and compounds that address oxidative stress and inflammation. Cinnamic acid derivatives, known for their neuroprotective properties, show enhanced efficacy when combined with established AD agents. The review highlights the adaptability and combinability of cinnamic acid as a basic structure, with methoxy substitutions at the para-position and electron-withdrawing groups showing increased efficacy. The molecular volume effect is also noted as worthy of further investigation. The article discusses the synthesis and evaluation of various cinnamic acid derivatives, including tacrine derivatives, isoquinoline and quinoline derivatives, benzylpiperidine derivatives, β-carbolines analogs, tryptamine derivatives, and rivastigmine derivatives. These compounds exhibit multifunctional activities, including AChE and BuChE inhibition, Aβ accumulation inhibition, antioxidant properties, and neuroprotective effects. The methoxy substitution at the para-position of cinnamic acid significantly enhances potency, while electron-withdrawing groups generally increase activity. The selectivity of the enzymes depends on the molecular volume, suggesting further investigation into this aspect. Overall, the review underscores the need for extensive research into cinnamic acid hybrids for the prevention and treatment of AD, given their promising multifunctional properties.