Objective: The research aimed to optimize the supercritical CO₂ extraction process of volatile oil from Perilla frutescens leaf and enhance the practical value of Perilla frutescens. Methods: The optimal parameters for extraction of volatile oil from Perilla frutescens leaf was predicted by single factor experiments （extraction pressure, extraction temperature, extraction time and CO₂ flow） and response surface methodology. Then the gas chromatography-mass spectrometry （GC-MS） was applied to determine the chemical components of volatile oil from Perilla frutescens leaf. In addition, its antioxidant activity was explored with the scavenging capacity on DPPH· and ·OH radicals. Results: The optimal process parameters of supercritical CO₂ extraction for volatile oil from Perilla frutescens leaf were founded to be at 27 MPa, 40 ℃ and 2 h, the actual yield was （2.71±1.19）%, which was 67% higher than the vapor distillation under the same extraction time and reduce the peroxide value and acid value. The 51 chemical compounds were identified in the volatile oil from Perilla frutescens leaf and accounted for 98.49% of all the peak area, which contained lipids, alcohols and olefins. The volatile oil of Perilla frutescens leaf had strong scavenging effect on DPPH· and ·OH radicals, and the scavenging capacity had a significant positive correlation with oil concentration. Conclusion: In this study, the supercritical CO₂ extraction of volatile oil from Perilla frutescens leaf were mainly composed of lipids, alcohols and olefins, which has strong antioxidant capacity.