Ethnopharmacological relevance: Andrographis paniculata (Burm.f.) Nees is widely used all over the world, especially in subtropical regions such as India, Thailand, Vietnam, and China. As a traditional folk Chinese medicine, A. paniculata has been extensively utilized for the treatment of cold, fever, sore throat, cough, carbuncle, and sores, and it is commonly employed for ‘clearing heat and resolving toxicity’. Typical symptoms of ‘heat and toxicity’ include swollen, painful gums, associated with virus-related diseases to a great extent. In vivo and in vitro experiments have demonstrated the potential antiviral properties of A. paniculata and identified its major active constituents against various viruses. Aim of the study: This review focuses on connecting the traditional ‘clearing heat and resolving toxicity’ effect to compelling recent research advances on the antiviral effects of A. paniculata, explaining its major antiviral mechanisms, and assessing the shortcomings of existing work. Besides, ethnobotany, ethnopharmacological uses, phytochemicals, and toxicology of A. paniculata have been researched. Materials and methods: The information about A. paniculata was collected from various sources including classic books about Chinese herbal medicine, and scientific databases including WEB OF SCIENCE, PubMed, ScienceDirect, Springer, ACS, SCOPUS, CNKI, CSTJ, and WANFANG. Results: In this review, the underlying mechanisms of antiviral effect mainly involve the regulation of virus entry, gene replication, and synthesis of functionally mature proteins. Also, A. paniculata is a safe agent without obvious toxicity. Ethnobotany, ethnopharmacological uses, and chemical constituents have been summarized. Conclusion: Andrographis paniculata (Burm.f.) Nees could be used as an imperative complementary medicine for the treatment of diverse virus infection, efforts should be made to gain insights into its antiviral properties.