The recent pandemics caused by coronavirus infections have become major challenges in 21st century human health. Scientists are struggling hard to develop a complete cure for infectious diseases, for example, drugs or vaccines against these deadly infectious diseases. We have searched papers on thymoquinone (TQ) and its effects on different infectious diseases in databases like Pubmed, Web of Science, Scopus, and Google Scholar, and reviewed them in this study. To date research suggests that natural products may become a potential therapeutic option for their prodigious anti-viral or anti-microbial effects on infectious diseases. TQ, a natural phytochemical from black seeds, is known for its health-beneficial activities against several diseases, including infections. It is evident from different in vitro and in vivo studies that TQ is effective against tuberculosis, influenza, dengue, Ebola, Zika, hepatitis, malaria, HIV, and even recent pandemics caused by severe acute respiratory syndrome of coronaviruses (SARS-CoV and SARS-CoV-2). In these cases, the molecular mechanism of TQ is partly clear but mostly obscure. In this review article, we have discussed the role of TQ against different infectious diseases, including COVID-19, and also critically reviewed the future use of TQ use to fight against infectious diseases.