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Isatis indigotica Fortune is a biennial Chinese woad of the Cruciferae family. It is primarily cultivated in China, where it was a staple in indigo dye manufacture till the end of the 17th century. Today, I. indigotica is used primarily as a therapeutic herb in traditional Chinese medicine (TCM). The medicinal use of the plant is separated into its leaves (Da-Qing-Ye) and roots (Ban-Lan-Gen), whereas its aerial components can be processed into a dried bluish-spruce powder (Qing-Dai), following dehydration for long-term preservation. Over the past several decades, I. indigotica has been generally utilized for its heat-clearing effects and bodily detoxification in TCM, attributed to the presence of several classes of bioactive compounds, including organic acids, alkaloids, terpenoids, and flavonoids, as well as lignans, anthraquinones, glucosides, glucosinolates, sphingolipids, tetrapyrroles, and polysaccharides. This paper aims to delineate I. indigotica from its closely-related species (Isatis tinctoria and Isatis glauca) while highlighting the ethnomedicinal uses of I. indigotica from the perspectives of modern and traditional medicine. A systematic search of PubMed, Embase, PMC, Web of Science, and Google Scholar databases was done for articles on all aspects of the plant, emphasizing those analyzing the bioactivity of constituents of the plant. The various key bioactive compounds of I. indigotica that have been found to exhibit anti-inflammatory, antimicrobial, anticancer, and anti-allergic properties, along with the protective effects against neuronal injury and bone fracture, will be discussed. Collectively, the review hopes to draw attention to the therapeutic potential of I. indigotica not only as a TCM, but also as a potential source of bioactive compounds for disease management and treatment.