ABSTRACT: Generally, essential oils and components of interest are extracted from plants using organic solvent, distillation, ultrasound and supercritical extraction methods. Ultrasonic extraction (UE) has the advantage of high efficiency, but its process is complicated and it has numerous variables. In this study, an L18-Hunter experimental design was applied for the first time to investigate the practicability of applying UE to Forsythia suspensa seed oil. Six potential high-risk variables, including numerical and non-numeric types, were obtained from the risk analysis and their impacts on global yield and antioxidant activity were screened. Furthermore, oils obtained by different extraction processes (i.e., UE, supercritical fluid extraction (SFE), soxhlet extraction (SE) and hydrodistillation extraction (HD)) were analyzed. A comparative study of these oils was characterized and compared by FT-IR, GC-MS and antioxidant activity. The obtained results show that the type of solvent, solvent-to-solid ratio, extraction power and time were the significant variables affecting the extraction yield, whereas antioxidant activity was only affected by the type of solvent. The regression coefficients of the yield and antioxidant activity models were 0.79 and 0.91, and the ANOVA of the models were 0.013 and <0.0001, respectively. Beta-Pinene was the main abundant component in the oils for the UE, SFE, SE and HD methods and the content was about 46%~52.4%. In conclusion, the L18-Hunter design could be used as an effective experimental design method for rapid screening of high-risk variables. Regarding extraction efficiency, chemical composition and biological activity, UE not only offered a robust Forsythia suspensa seed oil extraction process, but also provided a time- and cost-effective advantage to the food and pharmaceutical industry when compared to the SFE, SE and HD extraction processes.