Objective: We aimed to investigate the potential benefits and mechanisms of vitamin B12 and folic acid supplementation in obesity. Materials and methods: Thirty two Sprague-Dawley rats were separated into four groups, eight rats each: controls were fed normal diet (ND), obese controls were fed high fat diet (HFD) (60% of their diet as saturated fats), vitamin B12-treated rats were fed HFD concomitant with an injection of 1 mg/kg/day of vitamin B12 for 5 days in week, and folic acid-treated rats were fed HFD with a concomitant administration of 50 mg/kg day of folic acid e, all for 12 weeks. At the end of the experiment, behavioural tests were performed, and blood samples were gathered for lipid profiles, serum vitamin B12, folic acid, and BDNF. The hippocampus and hypothalamus were isolated for oxidative stress and BDNF testing. Results: Obese rats showed hypercholesterolemia, hypertriglyceridemia (TG), hyperleptinemia, elevated oxidative stress markers, and a decline in cognitive and behavioural test parameters. Obesity had a negative effect on BDNF levels in the blood, hypothalamus, and hippocampus, which was reversed by the administration of vitamin B12 and folic acid. Treatment with vitamin B12 resulted in a significant rise in BDNF levels, a decrease in serum total cholesterol and TG, and a significant improvement in cognitive functions and behavioural test parameters. However, while the folic acid improved cognitive function parameters and oxidative stress markers, it had no effect on the lipid profile and showed a non-significant increase in BDNF levels