Aim: To determine allele and genotype frequencies of genes influencing anti-epileptic drug therapy in Mexican-Mestizo (MM) healthy volunteers, and to evaluate whether these are different from those reported for other populations. Subjects & methods: Thirty-nine variants of CYP3A5, EPHX1, NR1I2, HNF4A, UGT1A1, UGT2B7, ABCC2, RALBP1, SCN1A, SCN2A and GABRA1 were genotyped in 300 MM healthy volunteers. Results: All studied alleles were presented in MM, except for seven UGT1A1 variants (*6–8, 14, 15, 27 and 29). Allele and genotype frequencies showed interethnic variations when compared with European, Asian and African populations. Allele frequencies of greater than 30% were observed in ten genes. Conclusion: The results presented regarding the frequencies and interethnic differences of these polymorphisms should be taken into account for future pharmacogenetic studies of anti-epileptic drugs in MM patients with epilepsy.