Red cabbage (RC), a cruciferous vegetable rich in various bioactive substances, can significantly reduce the risk factors of several chronic metabolic diseases, but its mechanism remains clear. Given that the relationship between diet, gut microbiota and health, a diet -induced mice obesity model was used to elucidate the effects of RC on gut microbial composition and interactions in mice. After 24-hour dietary intervention, high-fat (HF) diet and intake of RC led to increased Firmicutes/Bacteroidetes (F/B) ratios in the feces of mice. RC also reduced the relative abundance of Bifidobacteria, Lactobacillus and Akkermansia muciniphila in mice fed low fat (LF) diet. After 8-weeks dietary intervention, RC significantly changed the structure and the ecological network of gut microbial community. Particularly, RC inhibited an HF-diet induced increase of AF12 in mice, and this genus was positively correlated with body weight, low-density lipoprotein level and fecal bile acid of mice. Unclassified Clostridiales, specifically increased by RC consumption, was also found to negatively correlate with hepatic free cholesterol levels in mice. Overall, our results demonstrated that RC modulation of gut microbial composition and interactions is associated with the attenuation of HF diet-induced body weight gain and altered cholesterol metabolism of mice.