Plastic particles are common pollutants in our daily lives and cause a range of potential toxicities when ingested by living organisms. However, the complex morphology of plastic particles in the natural environment makes it difficult to assess their potential toxicity using conventional ecological monitoring techniques. Therefore, we constructed an electrochemical sensor based on gold/multi-wall carbon nanotube-Fe(III) meso-tetra (4-carboxyphenyl) porphyrin/Nafion (Au/MWCNT-FeTCP/Nafion) composite material to evaluate the potential toxicity of plastic particles through the detection of nitric oxide (NO). The sensor exhibited good catalytic performance for NO with a linear relationship within 0.1–––0.7 μmol/L and 0.8–––5 μmol/L and a detection limit of 0.08 μM. We used this sensor to evaluate the changes in NO released by cells and tissues exposed to polystyrene (PS) plastic particles which showed that as the concentration of PS incubated with cells increased and the incubation time prolonged, the level of NO released by cells also increased. Notably, we combined immunofluorescence, immunoblotting, and electrochemical analysis methods simultaneously to reveal the cellular signaling pathway of NO production and apoptosis induced by PS. Furthermore, the effectiveness of the sensor in biomonitoring the oxidative damage of PS plastic particles on NO was further verified at the tissue level by constructing a mouse model treated with PS plastic particles. The sensor presented here offers a promising approach to study the biotoxicity of plastic particles and may contribute to the development of novel solutions for mitigating their hazardous effects on the human health.