Obesity is related to energy imbalance and energy metabolism. In this study, we investigated the anti-obesity effects of Garcinia indica extract (GIE), Coleus forskohlii extract (CFE), and the combinations of these two extracts in a 3T3-L1 cells and high-fat diet (HFD)-induced obese mice. In vitro, GIE showed better effect on TG content than CFE, CFE showed better effect on glycerol released than GIE, and the combinations of GIE and CFE showed both effects compared with GIE and CFE alone. In vivo, GIE, LMIX (0.005% GIE + 0.025% CFE), and HMIX (0.01% GIE + 0.025% CFE) down-regulated adipogenesis-related transcription factors PPARγ and C/EBPα protein expression, CFE promoted lipolysis by up-regulated p-HSL and p-PKA protein expression, and four supplementations promoted fatty acid β-oxidation by up-regulating CPT-1A and PPARα protein expression to decrease lipid accumulation in adipose tissue. Moreover, we found that CFE, LMIX and HMIX, except GIE exert increasing the abundance of Bacteroides caccae compared with HFD group. Overall, GIE, CFE, and the combinations of GIE and CFE were able to decrease body weight and adipocyte size by promoting fatty acid β-oxidation and modulating gut microbiota in HFD-induced obese mice.