Global epidemic levels of obesity are frequently accompanied by life-threatening comorbidities. Since the traditional medicinal practices by local healers are safe and efficacious, the scientific community is forced to look into the indigeneous medicinal plants' potential due to the lack of long-term, safe and effective treatments for obesity in modern pharmacotherapy. The objective of this study was to investigate the ability of Alstonia scholaris (L.) R.Br. bark extract to prevent obesity in obese rats. Six experimental groups were included in this in vivo investigation. Rats in Group I, known as the normal control, received a normal rat ration only; rats in Group II, known as the obese control, received only a HFD; rats in Group III, known as the positive control, received a HFD with orlistat medication; and rats in Groups IV, V, and VI received 100, 300, and 900 mg/kg bw of ASBE, respectively, in addition to HFD. Diet and medicine were administered orally once daily for a duration of 45 days. After the experiment, several observations were made on physical, biochemical and histological parameters. In vivo investigations including the treatment of ASBE plant extract revealed notable effects on physical parameters, including body weight, food consumption and organ weight. A marked decrease in the organ and fat pad weights was observed by the histological investigation. Biochemical parameters such as the lipid profile, atherogenic index, glucose, insulin, leptin, hepatic antioxidant enzymes and inflammatory markers like IL-6 and TNF-alpha were observed and successfully brought back to normal serum levels. The study's observations conclusively proved that A. scholaris bark extract has strong antiobesity potential.