Sorghum bicolor plant has a high abundance of 3-deoxyanthocyanins, flavonoids and other polyphenol compounds that have been shown to offer numerous health benefits. Epidemiological studies have linked increased intake of S. bicolor to reduced risk of certain cancer types, including lung adenocarcinoma. S. bicolor extracts have shown beneficial effects in managing hepatorenal injuries. This study investigated the cytotoxic potential of three apigeninidin-rich extracts of S. bicolor (SBE-05, SBE-06 and SBE-07) against selected cancer cell lines and their ameliorative effect on aflatoxin B1 (AFB1)-mediated hepatorenal derangements in rats. We observed that, among the three potent extracts, SBE-06 more potently and selectively suppressed the growth of lung adenocarcinoma cell line (A549) (IC50 = 6.5 μg/mL). SBE-06 suppressed the expression of STAT3 but increased the expression of caspase 3. In addition, SBE-05, SBE-06 and SBE-07 inhibited oxidative and nitrosative stress, inflammation, and apoptosis and preserved the histoarchitectural networks of the liver and kidney of rats treated with AFB1. These in vitro and in vivo studies indicate the potential of these cheap and readily accessible extracts for cancer therapy and as chemo-preventive agents in preventing aflatoxin-related health issues.