The most challenging threat facing the global community today is the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite global efforts to develop suitable treatments, very few specific antiviral agents have been suggested and the virus remains a serious global health risk. In vivo animal experiments have demonstrated that bioactive mycochemical constituents of Inonotus obliquus have immunomodulatory, antimicrobial, and antiviral properties. The present study investigates the antiviral potential of I. obliquus terpenoids against COVID-19 using a molecular docking study. The in silico study elucidates the ability of most of the terpenoid components to interact with the receptor-binding domain of SARS-CoV-2 spike glycoprotein with excellent affinity. Additionally, we found that both betulinic acid and inonotusane C could bind and stably interact with the spike protein near the host cell recognition site of angiotensin-converting enzyme 2.