Obesity is one of the top ten adverse health conditions in the world and it has doubled in the last decades. Altered maternal nutrition, including both undernutrition and maternal obesity, have been shown to lead to transgenerational transmission of metabolic disorders in the offspring, perpetuating metabolic disorders in the future generations. Several interventions have been performed in animal models of obesity to reduce the long-term obesity-related sequelae and consequently the adverse effects on offspring’s health. Our aim was to critically review studies that performed interventions with natural/botanical compounds in rodent model high fat diet (HFD) induced obesity and to assess glucose, lipid, metabolic and cardiovascular outcomes. We carried out a computerized literature review using PubMed and Medline. We identified fourteen studies that fulfilled the inclusion criteria. Lipid profile, in term of adipogenesis, leptin, triglycerides, cholesterol and adiponectin levels, improved after administration of all the natural compounds tested. Glucose profile improved with the supplementation of rice hull smoke extract, rheum undulatum, zanthoxylum piperitum DC ethanol extract and alpinia officinarum showing an increased insulin sensitivity. Oxidative stress and body weight also improved after the supplementation with most of the compounds in rodent models of obesity, proving promising and effective anti-obesity properties. These experimental studies demonstrate that several natural interventions improve lipid, glucose and oxidative profiles in rodents presenting an obese phenotype induced by a high fat diet consumption. Clinical research could now explore the efficacy and safety of such interventions in the obese population to reduce the long-term sequelae of this metabolic disfunction and thus to interrupt the vicious circle that an obese mother generates a child prone to develop metabolic (and cardiovascular) disease in adult life.