Kawasaki Disease (KD) is a multisystemic vasculitis of unknown aetiology in children. The incidence of KD varies by geographic area and correlates with differences in gut microbiota patterns, with the highest incidence in Asian. This study aimed to investigate alterations in faecal microbiota and assess their relationship with systemic inflammation in KD patients. A total of 59 patients and 55 matched controls were included. Fecal samples were collected at the onset of KD. The V3/V4 regions of 16S rDNA were sequenced using the MiSeq platform. PICRUSt 2 was used to analyse the potential functional pathways involved in gut dysbiosis. Alpha (p < 0.042) and beta (p < 0.001) diversity in KD were significantly decreased when compared to the control group. After multivariate regression, among the seven critical microbes, increased Eggerthella lenta (p = 0.016) and decreased Bacteroides ovatus (p = 0.014) could also predict KD risk using receiver operating characteristic curve (ROC) analysis (Eggerthella lenta: area under the ROC curve, AUC = 0.841, odds ratio = 23.956; Bacteroides ovatus: AUC = 0.816, odds ratio = 31.365). Notably, Bacteroides ovatus was positively correlated with blood segment cells (p = 0.006), but negatively correlated with blood lymphocytes (p = 0.013). After multivariate regression, flavone and flavonol biosynthesis decreased in children with KD (p < 0.001). Our results indicated that both Bacteroides ovatus and Eggerthella lenta may deregulate flavone and flavonol biosynthesis, consequently modulating immune cells and potentially triggering KD. This study suggests that alterations in the gut microbiota are closely associated with immune responses and provides a new perspective on the aetiology, pathogenesis, and treatment of KD.