Alzheimer's diseases(AD) has been discovered and under research for more than 70 years, However there is no cure for these progressive and devastating diseases. Based on the following hypothsis: Aß metabolite problem/over production result in the accumulation, and lead to aggregation is the cause of Alzheimer’s disease. AApeptide and Melatonin derivatives can bind to Aß and block the aggregation of β amyloid monomers, decrease the toxicity of Aß to neurons and slow the progressive of Alzheimer’s diseases. In addition, AApeptide which mimic transmembrane peptide Tat will have similar transmembrane function. We have set up our goals as follows: 1) Using newly discovered peptidomimetics, AApeptides. We moved on to research to discover their potential of transmembrane activity and anti-Alzheimer's acitiviy. 2) In Addition, studies of small molecule melatonin derivatives were also progressed. Methods include in this research includes bioorganic synthesis, identification of spectroscopy and relative assays targeting on biological efficiency of Anti-Alzheimer’s diseases. The details of which will be described in Chapters. In conclusions, two sets of transmembrane peptidomimetics for drug transportation has been successfully evaluated and potential of AA peptide small molecules, melatonin derivativesare also evaluated. These works have gained good progress in research between AApeptide and Alzheimer’s Diseases. These works also established basis of research in developing peptidomimimetics as potential pharmacies against Alzheimer’s diseases.