Background: Mental Retardation (MR) is a genetic disorder manifested in childhood and is significantly characterized by decreased intelligence and adaptive skills. It is also the most common developmental disorder with overall below average intellectual functioning and deficits in adaptive behavior. MR in young children is often missed by clinicians. The condition is present in 2 to 3 percent of the population, either as an isolated finding or as part of a syndrome or broader disorder. Aim: The aim of the present study was to investigate the association of folate metabolizing gene variants MTHFR(C677T) & (A1298C); MTR(A2756G); MTRR(A66G); MTHFD1(G1958A) and RFC(A80G) in mental retarded (MR) cases and controls in North Coastal Andhra Pradesh. Methods: A total of 200 samples (100 MR cases and 100 controls) were included in the present study and genotyping was accomplished by using PCR - RFLP technique. Data was analyzed by SPSS software. Results: The odds ratio p value of the variant MTHFR C677T genotype CC and CT were statistically insignificant whereas TT genotype was found to be statistically significant. The odds ratio p value of the variant (A1298C) of MTHFR, MTR (A2756G), MTRR (A66G), and RFC1 (A80G) genes were not statistically significant with MR cases. The odds ratio p value of the variant MTHFD1 (G1958A) genotype AG was found to be showing small risk compared to AA and GG genotypes. Conclusions: The present study concludes that the MTHFR 677 C>T and MTHFDI genes shows association with MR and MTHFR 1298 A>C, MTRR A66G , MTR A2756G and RFC 1A80G genes does not shows any association with MR.