Obesity is a life-threatening metabolic disorder that predisposes individuals to other diseases. In this study, the effect of nisin, a bacteriocin produced by some bacteria, on an animal model of obesity based on selected parameters was investigated. Forty Swiss NIH mice were randomly divided into four groups and received either a placebo (saline) or nisin (25, 50, or 100 μg/kg, ip) daily for 8 weeks. The mice in all groups were fed a high-sugar diet throughout the experiment. Bodyweight and food intake were measured weekly, and at the end of the experiment, the levels of FBS, serum triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein, and hepatic enzymes were tested, and red and white blood cell counts, hemoglobin concentration, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were determined. Finally, the expression levels of some obesity-related genes, including stearoyl-CoA desaturase-1 (SCD-1), glucose transporter-4 (GLUT4), zinc finger protein 423 (zfp423), 422 (ap2), and tumor necrosis factor-alpha (TNF-α), were assessed using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). After the experiment, the body weights, abdominal fat, and body mass index were significantly lower in the nisin-treated groups than in the control group. The highest effect was observed with 50 μg/kg nisin. The expression of SCD-1, GLUT4, 422(ap2), and TNF-α decreased significantly following treatment with nisin. No significant differences were observed in the other studied parameters, and no toxic effects were observed for nisin under these experimental conditions. The results suggested that nisin could have antiobesity effects.