Obesity is a global health concern that requires urgent investigation and management. While synthetic anti-obesity medications are available, they come with a high risk of side-effects and variability in their efficacy. Therefore, natural compounds are increasingly being used to treat obesity worldwide. The proposition that naturally occurring compounds, mainly polyphenols, can be effective and safer for obesity management through food and nutrient fortification is strongly supported by extensive experimental research. This review focuses on the pathogenesis of obesity while reviewing the efficacy of an array of phytoactives used for obesity treatment. It details mechanisms such as enzyme inhibition, energy expenditure, appetite suppression, adipocyte differentiation, lipid metabolism, and modulation of gut microbiota. Comprehensive in vitro, in vivo, and preclinical studies underscore the promise of phytoactives in combating obesity, which have been thoroughly reviewed. However, challenges, such as poor bioavailability and metabolism, limit their potential. Advances in nanomedicines may overcome these constraints, offering a new avenue for enhancing the efficacy of phytoactives. Nonetheless, rigorous and targeted clinical trials are essential before applying phytoactives as a primary treatment for obesity.