The effect of the extract of Ligustrumn lucidum fruits (LFE) and its major secoiridoid (LFS), (8-E)-nüzhenide, on obesity was investigated using high fat-diet (HFD)-induced C58BL/6J obese mice. LFE and LFS were administered at the doses of 300 mg/kg and 30 mg/kg, respectively, for 6 weeks. The anti-obesity activity was evaluated by measuring body weight, epididymal fat and metabolic plasma parameters. On Day 42, the body weight of the LFS-treated group was significantly lower compared with the HFD-treated group. Body weight gain was also reduced by 23.2% and 32.0% in the LFE- and LFS-treated groups, respectively, compared with the HFD group. In addition, the weight of the epididymal fat in the mice was significantly decreased in the HFD+LFS group. The food efficiency ratios (FERs) of the HFD+LFE and HFD+LFS groups were also lower compared with the HFD group with the same food intake. Metabolic parameters that had increased in the HFD group were decreased in the HFD+LFE and HFD+LFS groups. In particular, the increased triglyceride values were significantly reduced in the HFD+LFS group. These results show that treatment with LFE and LFS decreased HFD-induced obesity, mainly by improving metabolic parameters, such as fats and triglycerides. Therefore, LFE and LFS have potential benefits in regulation of obesity.