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Development of green extractions of natural compounds is an ongoing challenge for researches. The aim of the study was to evaluate the extraction of bioactive compounds (BACs) from oregano combining an experimental procedure with a theoretical approach using two computational simulation methods, Hansen solubility parameters (HSP) and conductor-like screening model for real solvents (COSMO-RS) software. In this study, the high-voltage electrical discharge-plasma (HVED) was used as one of new promising green extraction techniques. Optimization of processing extraction parameters (argon and nitrogen for generation of plasma, voltage―15 kV, 20 kV, and/or 25 kV), frequency (100 Hz), pulse duration (400 ns), and treatment time (3 and 9 min) was done using software STATGRAPHICS. Oregano extracts were prepared by pharmacopoeia, 1 g per 50 mL of solvents (water or aqueous ethanol …