A new ionic liquid-based silica sorbent was developed by a process involving surface chemical modification of commercial silica using a synthesized ionic liquid. The obtained particles were successfully used as a special sorbent in a solid-phase extraction process to isolate liquiritin and glycyrrhizic acid from licorice. Different washing and elution solvents, such as water, methanol/water (v/v), and pure methanol were evaluated. Ionic liquid-based silica sorbent was compared with traditional C18 sorbent and it exhibited higher selectivity. Quantitative analysis was carried out by using a C18 column. Good linearities of two compounds were obtained from 5×10−4 to 0.2 mg/mL (r2>0.99) with the relative standard deviations <1.0%. The target compounds in commercial herbal medicines containing licorice were determined, and the bound rates between the target compounds and protein were obtained by this sorbent.