Obesity is a major health problem affecting not only adults, but also children worldwide. It is associated with several comorbidities, including type 2 diabetes mellitus (DM), hypertension, dyslipidemia, metabolic syndrome, cardiovascular diseases, and cancer. The present work aimed mainly to: Evaluate the biochemical effects of raspberry ketone (RK) either alone or in combination with CR or normal diet on modulating metabolic changes in obese rats. Results The findings of this study support the recent evidence suggesting the potential of the natural product RK as an effective intervention for the management of obesity complications through its supplementation with normal diet. Concomitant supplementation of RK with normal diet is equivalent to calorie restriction effect in reducing body weight and obesity related-metabolic changes as oxidative stress and inflammatory markers associated with improvement in the anti-inflammatory cytokine (adiponectin). Therefore, this study recommended such regimen to limit many of the adverse effects of obesity and increase the adherence of obese patients to this regimen rather than calorie restriction which suffers from unpleasant deprivation effect and rebound weight gain.