Obesity is a multifactorial chronic disease or syndrome mainly caused by an imbalance in energy expenditure and intake. Obesity and its associated complications make it the fifth leading cause of global mortality. The benefits of the current anti-obesity treatment regimen have been marked by high cost and numerous adverse effects. Therefore, many researchers focus on plant-derived/natural products or altered dietary patterns for the management of obesity and its related complications (co-morbidities). Several epidemiological studies have confirmed that the consumption of functional foods/nutraceuticals could considerably lower the risk of various chronic diseases, like obesity, diabetic mellitus, and cancer, but the underpinning mechanism is still unclear. This comprehensive review briefs on the prevalence of obesity, the complications related to obesity, the current treatment regimen and the importance of functional foods and nutraceuticals (molecular mechanism) for the management of body weight and alleviation of its co-morbid conditions. This is the first comprehensive review revealing the in-depth anti-obesity mechanisms of various popular functional foods and nutraceuticals with a special reference to randomized clinical trials (RCTs). Overall, this contribution highlights the importance and beneficial role of functional foods/nutraceuticals on weight management (anti-obesity) and their contributions to the current treatment status, especially related to clinical trials, which could help in the development of novel functional foods/nutraceuticals for combatting obesity and its co-morbidities.