It is broadly interesting but remains a big challenge to explore nanomaterials-based methods to enable naked-eye observation and determination of ultratrace biomarkers and drugs. In this study, we developed a straightforward and extendable plasmonic nanosensor to enable visually quantitative determination of ultratrace target molecules through combining the use of enzyme-mimetic gold nanoclusters (AuNCs). Starting from sandwiched antibody-antigen (i.e., an analyte)-antibody structure, we conjugated AuNCs on the outer layer antibody to catalyze the decomposition of hydrogen peroxide used to reduce HAuCl4 into gold nanopartilces (AuNPs) for naked eye readout. This strategy is in theory applicable to all immunoreactions available and the protocol proposed to attach AuNCs onto an antibody is suitable to all proteins. The applicability of this type of nanosensor was validated by the determination of various ultratrace analytes such as protein avidin, breast cancer antigen, thyroid hormone, and even methamphetamine (MA), giving a naked-eye-readout limit of detection (LOD), down to 1.0 × 10(-20) M protein avidin, 7.52 × 10(-14) U/mL breast cancer antigen 15-3, 2.0 × 10(-15) mg/mL 3,5,3'-L-triiodothyronine and 2.3 × 10(-18) mg/mL MA. This strategy is thus considered an ultrasensitive way to fabricate plasmonic nanosensors, having wide and invaluable application potential in clinical, biological, and environmental studies, and in food quality control.