Latin-American populations have been largely underrepresented in genomic studies of drug response and disease susceptibility. In this paper, we present a genome-wide Chilean dataset from Talca based on the Illumina Global Screening Array. This let us to compare the frequency of gene variants involved in response to drugs among our population and others, taking data from the 1000 Genomes Project. We found four single-nucleotide polymorphisms with low prevalence in Chileans when compared with African, Amerindian, East and South Asian, and European populations: rs2819742 (RYR2), rs2631367 (SLC22A5), rs1063320 (HLA-G), and rs1042522 (TP53). Moreover, two markers showed significant differences between lower and higher proportion of Mapuche ancestry groups: rs1719247 (located in an intergenic region in chromosome 15; p-value = 6.17 × 10−5, Bonferroni corrected p-value = 0.02) and rs738409 (A nonsynonymous gene variant in the PNPLA3 gene; p-value = 9.02 × 10−5, Bonferroni corrected p-value = 0.04). All of these polymorphisms have been shown to be associated with diverse pathologies, such as asthma, cancer, or chronic hepatitis B, or to be involved in a different response to drugs, such as metformin, HMG-CoA reductase inhibitors, or simvastatin. The present work provides a pharmacogenetic landscape of an understudied Latin American rural population and supports the notion that pharmacogenetic studies in admixed populations should consider ancestry for a higher accuracy of the results. Our study stresses the relevance of the pharmacogenomic research to provide guidance for a better choice of the best treatment for each individual in a population with admixed ancestry. © 2022 by the authors.European Commission, EC; Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT, (1220540, Nº11150022); Instituto de Salud Carlos III, ISCIII