Coronavirius disease 2019 (Covid-19) pandemic caused by SARS-Cov-2 has raised global health concern without approved drug for management of this lie threatening disease. The aim of this study was to predict the inhibitory potential of quercetin-3-o-rutinoside against SARS-Cov-2 spike glycoprotein. Targeting the SARS-Cov-2 spike protein from angiotensin converting enzyme 2 complex (pdb: 6lzg) is gaining importance. In this study, in silico computational relationship between plant-derived natural drug and spike glycoprotein was predicted. The results were evaluated based on glide (Schrodinger) dock score. Among the five (5) screened compounds, quercetin-3-o-rutinoside has the best docking score (-9.296) with the target. Molecular dynamic (MD) simulation study was performed for 1000ps to confirm the stability behavior of the spike protein and quercetin-3-o-rutinoside complex. The MD simulation study validated the stability of quercetin-3-o-rutinoside in the spike protein binding pocket as potent inhibitor.