In this study, we propose a novel strategy, plasma activated water (PAW) to reduce pesticide residues on agricultural products. To validate its feasibility and effectiveness, we employee high-performance liquid chromatography (HPLC) to detect phoxim on grapes. HPLC results suggest that the reduction of phoxim on grapes achieve 73.60% after treated 10 min by PAW prepared 30 min, and the concentration of phoxim decreased significantly (p < 0.05) with the preparation time of PAW. Furthermore, HPLC-MS analysis shows that the reduction effect of phoxim by PAW is dominated by the degradation of phoxim. Combined with analyzing the physicochemical properties of PAW, one possible degradation pathway is proposed under the present experimental conditions, mediated by reactive oxygen and nitrogen species. The acidic environment (pH < 3) and high oxidation capacity (ORP > 500 mV) are suggested to be a benefit to the reduction of phoxim. Besides, the experimental results regarding color, firmness, sugar, vitamin C, and superoxide dismutase of grapes demonstrate that the PAW treatment will not significantly affect the quality of grapes. In conclusion, phoxim pesticide residues on grapes could be effectively reduced by the PAW strategy and without a significant (p < 0.05) effect on grapes quality.