Context: In traditional medicine, Kesaraja (Ayurveda) or Manjal karisali (Siddha) is effective for jaundice. Aim: Three species of Asteraceae need to be studied for their therapeutic superiority of their intended claim. They are Wedelia chinensis (Osbeck) Merr. Philipp J., Wedelia trilobata (L.) Hitchc. and Eclipta prostrata (L.) L. (Asteraceae). The present study aimed to screen and characterize the potential species for therapeutic purpose. Materials and Methods: The whole plants, W. chinensis (Osbeck) Merr. Philipp J., W. trilobata (L.) Hitchc. and Eclipta prostrata (L.) (Asteraceae) were collected and botanically identified. Preliminary phytochemical analysis and high‑performance thin‑layer chromatography finger printing with marker wedelolactone were done for the ethanolic extracts of these plants. Botanical and pharmacognostical diagnostic characters of the plants based on macro‑morphological, micro-morphological and powder microscopical characterization were worked out. Comparative in‑vitro antioxidant potential of ethanolic extracts of these plant species was carried out. Using ADMET SAR software, the pharmacokinetics of wedelolactone were predicted. Using Autodock 4.2 software, the binding energy of wedelolactone on targets of acetaminophen‑induced hepatotoxicity namely PPAR‑α, AMPK, JNK‑1, EGFR, Nrf2, ALT, ALP, GGT, CAR, Frizzled receptor, FXR, ERK1, LXR, mitochondrial glutamate dehydrogenase, p53, mTOR C1, CYP1A2, CYP2E1, 5‑lipoxygenase, thrombin, UCP1, GSK1, RXR and PXR was predicted. Results: All the three plant species were pharmacognostically and chemically different. W. chinensis was found to possess more antioxidant potential than the other two plants. The marker compound wedelolactone was not detected in W. trilobata. Wedelolactone passed the Lipinski`s rule of five, and the docking analysis of wedelolactone confirmed high binding affinity toward PPAR‑α, AMPK, Nrf2, CYP2E1, EGFR, JNK1, UCP‑2, thrombin, 5‑lipoxygenase, mTORC1, RXR, FXR, LXR, Frizzled receptor, GDH and Erk‑1. Conclusion: Based on the above observations, we conclude that the presence of marker compound wedelolactone might have attributed the potency of W. chinensis and E. prostrata in counteracting acetaminophen toxicity when compared with W. trilobata.