Nowadays, many people were dying due to infectious coronavirus diseases (COVID-19). It belongs to the betacoronavirus family and also known as SARS-CoV-2. However, COVID-19 is a new form that has some basic difference in the genome which makes it more lethal and infectious. In transmitted in human in late December 2019 and it infected about 20 million till date. Its genome is composed of positive-sense single-stranded RNA, which encodes for the poly-protein. This poly-protein further cleaved into various components of the virus to make the numerous copy of the virus. There are many more similarities in their genome among the SARS-CoV-2, SARS-CoV, MERS-CoV. However, protease proteins are responsible for the cleavage and hence, COVID-19 main protease is a prime therapeutic target. To date, no medicine/ vaccine can fully cure their infection. To inhibit the activity of protease of COVID-19, molecular docking and ADMET studies of 116 noscapine derivatives were performed and the result was compared with 14 reputed antiviral drugs including chloroquine and hydroxychloroquine. The molecular docking result indicates a better binding in comparison of 14 reputed drugs. Further, the top six noscapines was taken into consideration for the pose analysis and ADMET studies. Finally, the top six noscapine was refined by ADMET properties to get the most potent one.