This study evaluated the anti-obesity properties of the methanol extract of Zingiber officinale leaves in Wistar rats. Thirty male rats were distributed into five groups, with six rats in each group, and different groups were treated with a normal fat diet (NFD), high-fat diet (HFD), HFD + orlistat (20 mg/kg) p.o, HFD + Zingiber officinale (200 mg/kg) p.o, and HFD + Zingiber officinale (400 mg/kg) p.o for fifty-six days. After all administrations, the animals were sacrificed by cervical dislocation, and various biochemical analyses were carried out. Results showed that there was a significant decrease (p < 0.05) in body weight and adiposity in the Zingiber officinale, NFD, and orlistat groups compared to the HFD control. However, there was no significant difference in the body weights of rats in the Zingiber officinale groups compared to the NFD control and orlistat groups. Furthermore, rats in the Zingiber officinale groups had normal lipid concentrations, antioxidant status, adipokines, cytokines, liver, kidney, and cardiac function parameters that were comparable to orlistat and normal control but in contrast with the HFD control. Findings from the study suggest that Zingiber officinale leaves have significant anti-obesity, antioxidant, and anti-inflammatory properties.