This study tested the anti-hyperlipidemic, hypoglycemic, hepatoprotective, and anti-inflammatory effects of whole pearl millet grain powder (MPG) and its ethanol extract (MPGethaolE) in obese rats fed a high-fat diet. The rats were divided into eight groups based on the treatments they received: control, high fat diet (HFD), HFD + MGE (25 mg/Kg), HFD + MPGethaolE (50 mg/Kg), HFD + MPGethaolE (100 mg/Kg), HFD + MPG (10%), HFD + MPG (20%), and HFD + MPG (30%). The final body weight, visceral, epididymal fat pads, and the liver weight were significantly decreased, in a dose-dependent manner, in HFD fed rats that were co-administered either the MPG powder or MPGethaolE. In the same line, serum levels of triglycerides (TGs), cholesterol (CHOL), and low-density lipoprotein-cholesterol (LDL-c), as well as fasting glucose, insulin, HOMA-IR, and serum levels of lipopolysaccharides (LPS), interleukine-6 (IL-6), interleukine-10 (IL-10), C-reactive protein (CRP), tumor necrosis factor (TNF-α), and adiponectin were progressively decreased while serum levels of high-density lipoproteins (HDL-c) were significantly increased when increasing the doses of both treatments. In conclusion, both the raw powder and ethanolic extract of MP have a comparative dose-dependent anti-obesity, hypoglycemic, hypolipidemic, anti-inflammatory, and anti-steatotic in HFD-fed rats.