Rationale: Radix scutellaria-Licorice drug pair (RSLDP), a frequently used herbal pair with the effect of clearing heat and detoxifying, is the commonly employed drug pair in TCM prescription for the treatment of COVID-19. Until now, the metabolism feature and anti-COVID-19 mechanism of RSLDP have not been fully elucidated. Methodology: In this study, a sensitive and rapid method was developed for the separation and identification of the absorbed constituents of RSLDP in the rat plasma by UHPLC-QTOF-MS. Besides, we optimized the conventional process ways of network pharmacology and proposed a new concept called target network pharmacology (T-NP). It used the absorbed constituents and the corresponding targets to generate compound-target network, and compare to the conventional network pharmacology, it could reduce the false positive results. Results: A total of 85 absorbed constituents were identified or tentatively characterized in dosed plasma,including 32 components in Radix Scutellaria,27 components in Licorice and 65 components in RSLDP. The results showed that the compatibility of Radix Scutellaria and Licorice increased the quantity of components in vivo. We found that 106 potential targets of 64 active compounds in RSLDP were related to COVID-19.And 12 targets (MAPK3,IL6,JUN,IL2,STAT3, AKT1,TNF,STAT1,EGFR,HSP9AA1,VEGFA,RELA) could be core targets for RSLDP in treating COVID-19. Conclusions: The metabolism feature of RSLDP in vivo was systematically uncovered. The combining use of the T-NP method could discover potential drug targets and disclose the biological processes of RSLDP, which will clarify the potential mechanisms of RSLDP in the treatment of COVID-19.