Obesity and its associated disorders, such as hyperlipidemia, have become a global issue following the consumption of unhealthy, high-fat, and high-carbohydrate foods, which burdens the economies and the health systems of human societies worldwide. This study aimed to evaluate the effect of oral consumption of 6-gingerol and L-arginine supplements on serum lipid profile (triglyceride, cholesterol, high-density lipoprotein, and low-density lipoprotein), obesity factors, insulin, corticosterone and testosterone hormones, and expression of neuropeptide Y (NPY) gene in high-carbohydrate diet (HCD) induced obese rats. Thirty rats in five groups were fed a diet specific to each group for 12 weeks and then treated with the oral administration of L-arginine (200 mg/day) and 6-gingerol (100 mg/day) for twelve weeks. The food and water intake and weight change were then measured. In addition, plasma glucose, triglyceride, cholesterol, high-density lipoprotein (HDL), very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and serum hormone levels, including corticosterone, testosterone, and insulin, were measured, and NPY, Y1, and Y5 receptor gene expression were recorded using real-time PCR. Administration of 6-gingerol and L-arginine decreased food intake, weight gain, glucose levels, insulin levels, and homeostasis model assessment-insulin resistance (HOMA-IR) index compared to the HCD control group. In addition, corticosterone and testosterone levels in the study groups showed a significant decrease (P