Obesity represents one of the most pressing public health challenges of the twenty-first century, affecting more than 650 million adults globally and contributing substantially to the burden of cardiovascular disease, type 2 diabetes mellitus, musculoskeletal disorders, and several malignancies. Current pharmacological interventions, including orlistat, naltrexone-bupropion, and glucagon-like peptide-1 receptor agonists, provide meaningful weight reduction in select populations; however, their clinical utility is frequently constrained by significant adverse effect profiles, high cost, and limited long-term tolerability. There is consequently a pressing need for the identification and development of safer, more accessible, and mechanistically diverse anti-obesity agents. Plant-derived compounds—encompassing polyphenols, flavonoids, alkaloids, terpenoids, dietary fibers, and saponins—have garnered considerable scientific interest as candidate therapeutics, owing to their structural diversity and multifaceted pharmacological properties. These phytochemicals exert anti-obesity effects through several converging mechanisms, including the inhibition of pancreatic lipase activity, suppression of adipogenesis via peroxisome proliferator-activated receptor gamma downregulation, activation of AMP-activated protein kinase, enhancement of thermogenesis through uncoupling protein-1 induction, appetite modulation via incretin and leptin signaling pathways, and prebiotic modulation of intestinal microbiota composition. Preclinical evidence from both in vitro and rodent models is substantial; however, the translational path to clinical application remains challenged by poor bioavailability, lack of standardization, and limited Phase II and III trial data. This review critically examines the mechanistic basis, preclinical landscape, clinical evidence, and formulation strategies for plant-derived anti-obesity compounds, and provides a synthesis of future directions for their development as evidence-based therapeutics.