This study is the first to explore the effects of the novel yellow pigment monascinol (Msol) from red mold rice (RMR) on reducing body fat and to compare its effects with those of monascin (MS) and ankaflavin (AK). In a high-fat diet-induced rat model, different doses of RMR fermented rice (RL, RM, RH) and purified Msol, MS, and AK were administered over an 8-week period. The results showed that all treatment groups significantly reduced body weight and fat mass. Msol, in particular, activated acetyl-CoA carboxylase (ACC), inhibiting fatty acid synthesis and reducing triglyceride accumulation. All treatments suppressed the differentiation of preadipocytes into mature adipocytes by inhibiting CCAAT/enhancer-binding proteins β (C/EBPβ) and C/EBPα, as well as peroxisome proliferator-activated receptor γ (PPARγ). In the liver, RL, RM, RH, MS, and AK enhanced the expression of AMP-activated protein kinase (AMPK), ACC, peroxisome proliferator-activated receptor α (PPARα), and carnitine palmitoyl transferase-1α (CPT-1α), thereby promoting fatty acid metabolism. Additionally, RMR and its active components, MS and Msol, reduced body fat by modulating gut microbiota. These compounds significantly decreased the abundance of bacteria associated with fat storage, such as Oliverpabstia intestinalis, while increasing the abundance of bacteria linked to energy expenditure and lipid breakdown, such as Akkermansia muciniphila and Ruminococcus callidus. Moreover, MS and Msol upregulated proteins involved in fat degradation, such as UCP1, thereby enhancing fat burning and reducing fat accumulation. These regulatory effects suggest that Monascus and its components have potential in managing metabolic health and reducing obesity.