Sulfate-Reducing Bacteria (SRB) are a heterogeneous group of oral microflorae that cause dental caries, destructive periodontal infections, and biofilms on fixed orthodontic appliances. Plant extracts as a source of antibacterial components may have acceptable activity against SRB strains and their biofilm development. Our study aimed at determining the antibiofilm, antimicrobial efficacy, and cytotoxicity of Iran's endemic plants against pathogenic SRB. Plantago ovata, Terminalia chebula, Eugenia caryophyllata, and Aloe vera extracts were prepared according to standard methods. Patients and orthodontic appliances samples were collected, and SRB strains were isolated using standard tests and 16S rRNA analysis. The extracts' antimicrobial, antibiofilm activity, and cytotoxicity were determined using dilution broth micro, crystal violet staining, and MTT method, respectively. Biofilm involved gene expression of strains determined using Real-time PCR. Three SRB isolates harboring target genes were identified using 16S rDNA that showed a more than 90% of similarity to Desulfomicrobium orale spp. All investigated extracts showed good activity against SRB isolates. T. chebula, E. caryophyllata, and A. vera showed promising antibiofilm activity, and their subMIC concentrations downregulated biofilm-forming related genes in all isolates. T. Chebula had the lowest cytotoxicity, followed by E. caryophyllata and A. vera. T. Chebula also showed the best average selectivity index (SI) of 17.9, followed by E. caryophyllata (12.52). Extracts investigated in the present study had good antibacterial and antibiofilm activity against isolated sulfate-reducing bacteria isolated from patients' orthodontic appliances. Most of these extracts may be potential candidates for the development of antibacterial drugs.