Background: Vernonia amygdalina is traditionally used to treat a variety of diseases including diarrhoea, fungal and bacterial infections, inflammation, cancer, diabetes, and its squeezed juice can be applied on wounds. Objective: This study reviewed the phytochemistry, ethnopharmacological, and pharmacological potentials of V.amygdalina. Methods: Literature search of relevant papers (1994-2021) were performed using ScienceDirect, Springer, Wiley and PubMed databases. For this review study, only publications written in English were utilized. Results: The bioactive compounds extracted from V. amygdalina includes 6??,10??,14?? trimethylheptadecan-15 ??-olyl-15-O-??-D glucopyranosyl-1,5 ?? olide, glucuronolactone, 11 ??-hydroxyurs-5,12-dien-28-oic acid-3 ??,25-olide, 10-geranilanyl-O-??-D-xyloside, 1-heneicosenol O-??-D-glucopyranoside, apigenin, luteolin(3′,4′,5,7tetrahydroxyflavone), vernolide, hydroxyvernolide, 3′-deoxyvernodalol , vernodalol, diterpene(ingenol-3-angelate), vernomygdin, 4-methylumbelliferone, cephantharin, cryptolepine, isocryptolepine,neocryptolepine, courmarins, vernolepin, and vernoniosides. Various in vivo and in vitro studies revealed that V. amygdalina and its bioactive components possess pharmacological activities such as antioxidant,anti-inflammatory, anticancer, antimicrobial, hepatoprotective,antidiarrheal, anti-diabetic, and neuroprotective activities.Conclusion: This review demonstrated that V. amygdalina possess therapeutic effects against a wide variety of diseases. The efficacy of V. amygdalina in ameliorating diseases is attributed to its antioxidant activity and ability to improve the antioxidant system. Despite the vast pharmacological activities of V. amygdalina, more human clinical trials are needed to identify effective and safe doses for treatment of various diseases.