OBJECTIVE: This study aimed to uncover the microbial and metabolic changes in dental plaque during orthodontic treatments with fixed appliances (FAs) and clear aligners (CAs). MATERIALS AND METHODS: Twenty participants were grouped by the treatment modality they received, with 10 participants each in the FA and CA groups. Supragingival plaques were collected before orthodontic treatment (T0), after 1-3 months (T1) and more than 6 months (T2) of orthodontic treatment. 16S rRNA gene sequencing and liquid chromatography-tandem mass spectrometry were employed to analyse the plaque samples. RESULTS: No significant change was observed in the alpha and beta diversity at different time points and between the two treatment modalities. The relative abundance of genera Veillonella, Mogibacterium and unclassified_c__Actinobacteria, and species Actinomyces massiliensis , Prevotella pallens and Prevotella jejuni experienced the most significant changes. The most differential metabolites were amino acids, nucleosides and organoheterocyclic compounds. Compared to T0, downregulation of nucleotide metabolism at T1 and upregulation of amino acid metabolism at T2 were found in the FA group. Compared with the FA group, the CA group experienced metabolite enrichment in several immune pathways at T1, while linoleic acid metabolism, riboflavin metabolism and nucleotide metabolism were downregulated at T2 in the CA group. Significant correlations were identified between most differential plaque microorganisms and metabolites. CONCLUSION: This study implied that exposure to FAs for more than 6 months resulted in the accumulation of oral disease-related bacteria in dental plaque and a metabolic shift towards a cariogenic state, whereas CAs could lead to a transient proinflammatory state.