A simple signal‐on plasmonic optical assay for the detection of the Parkinson biomarker using gold‐nanoparticle clusters (AuNCs) for signal amplification is presented. This approach is based on the improvement of the optical density (OD) change of the plasmonic band of a localized surface plasmon resonance (LSPR) Au nanoparticle (AuNP) sensor interface using Au NCs conjugated antibodies. The amplification results in a 260‐fold improvement in concentration detection, from 1,000 ng/mL (unlabeled antibody) to 3.8 ng/mL (antibody‐conjugated AuNCs). The sensitivity enhancement can be ascribed to the further plasmonic coupling between the antibody‐conjugated AuNCs and the AuNPs on the LSPR interface and the enhanced amount of target molecule bound to the bioassay. This AuNCs‐assisted signal amplification strategy allows for improving the sensitivity of the plasmon‐based bioassays and can be extended to other optical‐based diagnostic technologies. Importantly, the simple detecting procedure and protocol assembly make it competitive with other existing sensing technologies such as ELISA, allowing for practical usage in clinical diagnostics.