The aim of this study was to evaluate the role of taste-related gene polymorphisms (CA6,TAS1R1,TAS1R3, TLR2,andTLR4)on dental caries and caries activity in adults. Individuals aged 25-44 years included in the study were assigned to two groups according to the decayed-missing-filled teeth index (DMFT) as the high caries risk (DMFT >= 14,n = 100) and the low caries risk (DMFT <= 5,n = 100). TaqMan allelic discrimination assays were used for genotyping the gene variants after isolating the DNA from the buccal smears. According to the American dental association caries classification system (ADA CCS), all teeth were scored as initial, moderate or advanced caries. The variant of the gustin (CA6) in saliva was found to be associated with a high caries risk (CA6rs17032907,P < .001). There was also a statistically significant difference in the dominant model of the same variant (CC vs. TT:P < .001, OR = 5.05, 95% CI: 2.38-10.71). The presence of genotype CC and allele C was less frequent in the advanced caries lesion group (P < .001). This study shows that theCA6rs17032907 gene variant may be a risk factor for dental caries affecting caries activity. Clinical Trials ID: NCT04066101.