The alpha synuclein (α-syn) oligomer is one of the biomarkers used for the early diagnosis of Parkinson's disease. In this paper, two electrochemiluminescent (ECL) biosensors with an aptamer as the recognition element for α-syn oligomer detection were prepared. A functionalized indium tin oxide (ITO) glass with metal–organic framework (MOF) materials provides an adequate sensing platform. Here the gold nanoparticles/metal organic frameworks (MOFs) composite (AuNPs@MOFs) using 3-aminopropyltrimethoxysilane as a binding agent, or to connect the MOFs onto the ITO directly via glutaraldehyde, both give a strong ECL emission for luminol, even under weak alkaline conditions. Thereafter, the thiolated or carboxylated aptamer was coalesced onto the MOF material functionalized electrode using an Au–S bond or amide bond via the classic 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide (EDC-NHS) coupling, respectively. Thus, the ECL emission of the sensors significantly reduced after the specific binding of the α-syn oligomer to the aptamer. The good linear relationship of the ECL sensing signals upon the logarithm of the α-syn oligomer concentration were established, from 2.43 fM to 0.486 pM or 1.39 fM to 0.243 pM, and the limit of detection reached as low as 0.42 or 0.38 fM, for these two sensors. Both of the obtained sensors have the advantages of a high sensitivity, selectivity, and reproducibility and are capable of detecting the target in human serum.