Since the outbreak of Coronavirus disease (COVID-19) caused by SARS-CoV-2 in December 2019, there has been no vaccine or specific antiviral medication for treatment of the infection where supportive care and prevention of complications is the current management strategy. In this work, the potential use of medicinal plants and more than 16 500 of their constituents was investigated within two suggested therapeutic strategies in the fight against SARS-CoV-2 including prevention of SARS-CoV-2 RNA synthesis and replication, through targeting vital proteins and enzymes as well as modulation of the host's immunity through production of virulence factors. Molecular docking studies on the viral enzymes 3Clpro, PLpro and RdRp suggested rocymosin B, verbascoside, rutin, caftaric acid, luteolin 7-rutinoside, fenugreekine and cyanidin 3-(6′′-malonylglucoside) as promising molecules for further drug development. Meanwhile, the medicinal plants Glycyrrhiza glabra, Hibiscus sabdariffa, Cichorium intybus, Chrysanthemum coronarium, Nigella sativa, Anastatica hierochuntica, Euphorbia species, Psidium guajava and Epilobium hirsutum were enriched in compounds with the multi-targets PTGS2, IL2, IL1b, VCAM1 and TNF such as quercetin, ursolic acid, kaempferol, isorhamnetin, luteolin, glycerrhizin and apigenin. Enriched pathways of the molecular targets included cytokine–cytokine receptor interaction, TNF signaling pathway, NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, NF-kappa B signaling pathway and JAK-STAT3 signaling pathway which are all closely related to inflammatory, innate and adaptive immune responses. The present study identified natural compounds targeting SARS-CoV-2 for further in vitro and in vivo studies and emphasizes the potential role of medicinal plants in the mitigation of SARS-CoV-2.