Flavonoid-rich plant compounds are known for their beneficial multi-health functions. The liver and kidney protective potentials of fresh lime juice (FLJ), 50% FLJ and 50% honey combination (MIX), and the methanol flavonoid-rich fraction of lime juice (MFLJ) were examined in this study. Three sets of eighteen male neonatal Wistar rats (phase 1) were utilized, totaling fifty-four. Rats in group III were given a diet rich in protein for 14 days, and those with a Lee index of 0.3 or higher were classified as obese. In group II, obesity was created by intraperitoneal injection of 5 mg/kg body weight of monosodium glutamate (MSG). Rats were rearranged into seven groups of six (phase II), and FLJ, MIX, and MFLJ were administered. Characterizing the flavonoids in MFLJ involved the use of high-performance liquid chromatography (HPLC). Gallic acid, caffeic acid, p-coumaric acid, sinapic acid, and quercetin—all of which provide hepato-renal protection—were discovered in MFLJ during HPLC analysis. Comparing obese rats to control and AOI rats, the body weight, food intake, adiposity index, and weight of liver, kidney, and heart all decreased considerably (p < 0.05) following FLJ, MIX, and MFLJ therapy. When compared to AOI and control rats, FLJ, MIX, and MFLJ therapy significantly (p < 0.05) improved the liver, and kidneys functions, and restored normal architecture of adipose, and hepatic tissues in obese treated rats. Obviously, these flavonoids in MFLJ could serve as model pharmacotherapy for the treatment and management of hepatic and renal dysfunction in obesity.