OBJECTIVES: In utero, exposure to maternal high-fat diet (HFD) has been identified to predispose the offspring to obesity and other metabolic dysfunctions later in life. Zingerone, a bioactive phytochemical found in ginger has potential for the treatment of metabolic diseases due to its antioxidant properties. This study investigated its potential reprogramming effect on some metabolic indices and pro-opiomelanocortin (POMC) gene in young adult offspring of Wistar rat models exposed to maternal HFD. METHODS: 30 pregnant Wistar rats were divided into five groups: Normal control group, an HFD control, and three experimental groups treated with 50, 100, or 200 mg/kg of zingerone, respectively. The treatment commenced from day 1 of pregnancy until postnatal day (PND) 21, after which the offsprings were weaned and placed on a standard diet until PND 42. On PND 42, the biochemical assays were performed on the offsprings using enzyme-linked immunosorbent assay kits and the hypothalamic POMC gene expression using reverse transcription polymerase chain reaction. Data were analyzed using analysis of variance. Values of P < 0.05 were taken as statistically significant. RESULTS: Offsprings in the zingerone-treated groups showed significant (P < 0.05) decrease in body weight, glucose, insulin, cholesterol, triglycerides, and leptin levels compared to the HFD control group. Food intake and ghrelin levels increased, while POMC gene expression was inhibited with 100 and 200 mg/kg of zingerone. CONCLUSION: Maternal zingerone administration may mitigate the risk of metabolic disorders in the offspring, possibly by its influence on the anorexigenic genetic makeup of the offspring.