This study was performed to evaluate the interplay between dental caries, nutritional status, and genetic polymorphisms in TAS1R1 and TAS1R2 (taste receptor, type 1, member 1 and 2) in preschool children and pre-adolescents. We included 525 subjects (306 preschool children and 219 pre-adolescents). Parents/caregivers answered a self-administered questionnaire about their children's systemic health, characteristics, oral hygiene habits, and diet. Clinical examination was performed to evaluate dental caries and nutritional status. Saliva samples were collected for DNA extraction. The genotyping of rs17492553 ( TAS1R1 ), rs3935570, and rs4920566 ( TAS1R2 ) polymorphisms was performed using real-time PCR with Taqman Genotyping Master Mix and SNP assay. Both univariate and multivariate Poisson regression analyses with robust variance were used for the data analysis. In preschool children, consumption of sweets between meals increased the prevalence of dental caries by 85% (PR c = 1.85; 95%CI 1.39-2.46; p < 0.001), whereas in pre-adolescents, this prevalence increased by 34% (PR a = 1.34; 95%CI 1.11-1.62; p = 0.002), regardless of genetic polymorphisms . Moreover, individuals carrying at least one allele C in rs17492553 presented 23% more prevalence of dental caries (PR a = 1.23; 95%CI 1.02-1.49 p = 0.030). Nutritional status was not associated with dental caries, neither with genetic polymorphisms . Consumption of sweets between meals increased the prevalence of dental caries. In pre-adolescents, rs17492553 genetic polymorphism in TAS1R1 was associated with dental caries.