Background In the presence of a stimulus that disrupts homeostasis, the body elicits a response known as inflammation. The inflammatory response is expected to restore the normal functioning of the body and initiate healing where necessary. However, the persistent activity of acute inflammation results in chronic inflammation which causes adverse consequences associated with diseases such as diabetes and arthritis. In traditional medical practice, Vernonia amygdalina is used to treat several ailments such as malaria, fever, diabetes, and inflammatory conditions such as those related to pain and swelling. Objective This review seeks to explore and discuss the therapeutic benefits of V. amygdalina in the treatment of inflammation and its associated diseases. Methods We reviewed the scientific literature indexed in PubMed, ScienceDirect and Springer, and discussed the reported anti-inflammatory properties of V. amygdalina and its curative activity in inflammation-associated diseases. Results A total of 30 published articles were identified describing the therapeutic effect of V. amygdalina in predominately experimental models. The anti-inflammatory properties of V. amygdalina have been linked to the presence of bioactive phytoconstituents predominantly present in the leaves of the plant. Conclusions Multiple studies have demonstrated that the aqueous and ethanolic extracts of V. amygdalina can inhibit the production of proinflammatory cytokines and enzymes in inflammatory cells, reducing inflammation and its associated complications. We critically appraise the current evidence, and discuss the potential use of this medicinal plant in the treatment of inflammatory conditions.