Justicia carnea, a plant rich in bioactive compounds, has traditionally been used as a haemoglobin booster by herbal practitioners in rural areas of Edo State of Nigeria. In this study, the methanol leaves extract of Justicia carnea was investigated for its antisickling potential in hemoglobin SS (HbSS) in-vitro by sodium metabisulphite assay and characterized by Gas Chromatography-Mass Spectrometry (GC-MS) and High-Performance Liquid Chromatography (HPLC). Terpenoids, saponins, glycosides, phenolics, flavonoids and alkaloids were present except tannins. Photomicrograph examinations revealed a reduction of (...) sickle cells with a percentage decrease from 37.50%, and 22.22% down to 3.85% with 100 mg/mL crude extract of Justicia carnea at three durations, respectively. Detected compounds from Gas Chromatography-Mass Spectrometry included hexadecanoic acid methyl ester (Retention time (Rt): 21.46, 05.99%) and 9,12-octadecadienoic acid, methyl ester (Rt: 23.567, 02.59%) while the major constituent was phytol (Rt: 23.741, 67.28%). While kaempferol (Rt: 17.23, 16.72%) was the major component from High-Performance Liquid Chromatography quantification among resveratrol (Rt: 3.7, 13.85%), gallic acid (Rt: 5.88, 3.55%), Justicinol (Rt: 11.85, 01.34%) and phytic acid (Rt 5.06, 01.43 %). These compounds have been cited as physiological agents that reduce inflammation, and oxidative stress and potentially prolong the lifespan of cells across species. The antisickling results from this study corroborate and support the traditional use of the plant in treating patients with sickle cell anemia. (shrink)