Alzheimer’s disease (AD) is the most common form of dementia and a challenging disease. It is characterized by cognitive decline, memory loss, and behavioral problems. The pathogenesis of AD is complex, and the molecular mechanisms and mechanisms involved in this devastating neurodegeneration are numerous. The development of small molecules targeting tauopathy and the search for antibodies are promising for the future of AD treatment. Here, we consider small-molecule therapeutics as a promising tool for the development of new drugs for the treatment of AD. Small molecules exhibit better shelf life, easier to handling and distribution, cheap, making them more suitable over the monoclonal antibodies. This review develops structural insight into the small molecules which have shown potential in drug development inhibiting acetylcholinesterase (AChE) in the treatment of AD. It may help the study of AD pharmacokinetics using small molecules, including new drug development, immunology, and clinical trial challenges.