Sorghum bicolor, locally called ‘Dawa’ (Hausa) and ‘Oka-pupa’ (Yoruba), is a widely cultivated cereal crop, mostly in northern Africa and other tropical regions. Beyond being a staple cereal, the sheath leaves have long been used in traditional medicine as a natural blood booster for treating and managing anaemia and general weakness. The use of the leaves' sheath in blood enhancement suggests its potential as a functional nutraceutical capable of improving human health and workforce productivity. This study aimed to investigate the phytochemical constituents and haematological parameters of rats fed Sorghum bicolor methanol leaf sheath extract and to use computationally assisted predictive interpretation to evaluate Sorghum bicolor sheath as a natural blood-boosting nutraceutical. The crude extract was subjected to fractionation and isolation using vacuum liquid chromatography and preparatory thin-layer chromatography, and the isolate recovered was characterised by gas chromatography mass spectrometry (GC-MS). 24 rats were divided into four groups. Group A served as control, while Groups B, C, and D received 1.0 mg/kg, 2.0 mg/kg, and 3.0 mg/kg of methanol sheath extract treatment, respectively, for 14 days. Full blood count parameters were analysed at the end of the treatment period using an automated haematology analyser. Saponins, glycosides, flavonoids, and alkaloids were among the phytochemicals present. The red blood cells, haemoglobin, and packed cell volume were within normal values, except the platelet count, which was the lowest for the low dose (1.0 mg/kg) group. The GC-MS analysis indicated oleic acid (Retention time (R_t): 15.91 min, 46.02 %) as the most abundant compound, suggesting the presence of a monounsaturated fatty acid. The study highlights that Sorghum bicolor extract contains diverse phytochemicals necessary for blood health. An evaluation of 22 test compounds showed superior drug-likeness compared to folic acid as the standard drug, with all compounds complying with Lipinski’s rule of five and possessing favourable molecular weights. High lipophilicity and high binding affinities suggest potential efficacy and low gastrointestinal absorption, necessitating specialised delivery mechanisms to overcome solubility challenges.