Abstract Craniofacial microsomia (CFM) is the second most common congenital craniofacial deformity, presenting diverse clinical manifestations and treatments that may influence oral bacteria dysbiosis (OBD). However, research linking CFM to OBD is limited. Saliva samples were collected from 20 patients with CFM and 24 controls. We compared oral microflora and gene function using 16 S ribosomal RNA sequencing and metagenomics. We also evaluated the correlation between CFM clinical phenotypes and microbiota community structure. Patients with CFM demonstrated greater richness and evenness in their oral microflora. The dominant genera included several pathogenic species, such as Actinomyces, Fusobacterium, and Prevotella. Notably, the severity of CFM correlated positively with the abundance of Neisseria and Porphyromonas. Upregulated pathways were primarily linked to biotin and amino acid metabolism, such as Tryptophan metabolism and Lysine degradation, and further underscored the need for focused oral health interventions in this population. This study is the first to indicate that CFM patients exhibit unique oral bacterial dysbiosis, marked by a higher presence of opportunistic pathogens and increased pathways related to oral and systemic health. These findings highlight the importance of monitoring oral health in patients with CFM.