Andrographis is a member of the family Acantheceae. It contains approximately 44 accepted species. Among them, Andrographis paniculata has been extensively studied during the last decade. The genus contains triterpenoids as the main class of compound, along with carotenoids, flavonoids, glycosides, xanthones, phenolic compounds, and fatty acid compounds. A. paniculata has been reported in Ayurveda, homeopathy, naturopathy, and Siddha. Traditionally, the genus is utilized in treating diarrhea, parasitic problems, liver illness, various skin problems, fever, snake bites, cough and many more. Pharmacological activities like antioxidant, neuroprotective, anti-inflammatory, antimalarial, hepatoprotective, antibacterial antiviral, anticancer, and antidiabetic have been documented in it with scientific evidence. Various components found in this genus show broad biological opportunities for novel medicinal medicines. Andrographolide is the major chemical constituent present in almost all the species. It has been reported for various pharmacological activities, mostly for antioxidant and anticancer. The genus is widely spread among India, China, Southeast Asia, Sri Lanka, Vietnam, Thailand, and basically tropical and subtropical Asia. In India, it is found in Nallamala Hills, Andhra Pradesh, and South India. The present review has provided a critically analyzed vision of phytochemistry, traditional uses, and pharmacological applications of the genus Andrographis. The current information was collected systematically from scientific databases, including Google Scholar, PubMed, ACS Publications, SciFinder, Science Direct, and Web of Science. DOI:10.2174/0113852728327331240905094331