Coffee consumption is associated with reduced risk of metabolic syndrome, obesity and diabetes. Although the mechanisms of action are not yet elucidated, the effects of coffee and its bioactive components on lipid metabolism may account for the overall coffee effects on human health. Therefore, this study investigated the molecular mechanisms of coffee and its bioactive components on lipid metabolism using Caenorhabditis elegans as a model system. Green coffee bean extract (GCBE), the chlorogenic acid 5-O-caffeyolquinic acid (5-CQA), and the coffee diterpenes cafestol and kahweol reduced fat accumulation via distinct lipid metabolism pathways and/or behavior changes in C. elegans. The fat-lowering effects of GCBE and 5-CQA were similarly dependent on sterol regulatory element binding protein (sbp-1) and forkhead box O (daf-16), both involved in lipogenesis, while cafestol reduced fat accumulation dependent on the FXR homolog, daf-12, in C. elegans. Moreover, cafestol increased worm’s moving speed, an indicator of energy expenditure. The effects of cafestol on energy expenditure was also dependent on tub-1 (homolog of the human TUBBY proteins), which it is likely to be a downstream target for DAF-12 in C. elegans. The other coffee diterpene, kahweol, also reduced fat accumulation, but instead kahweol’s fat-lowering effects were related to a reduced food intake in C. elegans. The effects of kahweol on lipid metabolism involved the downregulation of the insulin-like receptor daf-2, known to be regulated by food intake. Therefore, the suggested mechanisms of the effects of coffee bioactives on lipid metabolism may be applied for human health corroborating with the fact that consumption of coffee is associated with lower risk of obesity.