To determine the effects of a [6]-gingerol analogue (6G), a major chemical component of the ginger rhizome, and its stable analogue after digestion in simulated gastric fluid, aza-[6]-gingerol (A6G), on diet-induced body fat accumulation, we synthesized 6G and A6G. Mice were fed either a control regular rodent chow, a high-fat diet (HFD), or a HFD supplemented with 6G and A6G. Magnetic resonance imaging adiposity parameters of the 6G- and A6G-treated mice were compared with those of control mice. Supplementation with 6G and A6G significantly reduced body weight gain, fat accumulation, and circulating levels of insulin and leptin. The mRNA levels of sterol regulatory element-binding protein 1c (SREBP-1c) and acetyl-CoA carboxylase 1 in the liver were significantly lower in mice fed A6G than in HFD control mice. Our findings indicate that A6G, rather than 6G, enhances energy metabolism and reduces the extent of lipogenesis by downregulating SREBP-1c and its related molecules, which leads to the suppression of body fat accumulation.