Recent studies have enlightened the complexity of the genetic landscape present in New Guinean populations. From the New Guinean genome, inherited from the Out-of-Africa dispersal 60 000 years ago, to the gene flows from Austronesian groups during the Holocene, and even to the high percentage of genetic introgression from an extinct Homo species named Denisova, the biological diversity of New Guineans is unique. It is a result of the various human migrations to the island but also within its territory, composed by a variety of different ecosystems. These processes created high genetic differentiations between New Guinean groups, a pattern that superficially mirrors the one drawn from the linguistic diversity, one of the highest in the world, with more than 900 languages. Despite these results, major issues remain unresolved regarding New Guinean genetic history. Since 2016, thanks to the French Ministry of Foreign Affairs and the University of Papua New Guinea, we have developed an international and interdisciplinary research project aiming to reconstruct the demographic and adaptive history of New Guinean populations. A particular focus is put on the interaction between the New Guinean and Non-New Guinean genetic diversities, and how this mirror the highland and lowland division and the main New Guinean language families distribution, in structuring the current human biological landscape of the island. In this paper we will present results based on the analysis of whole-genome sequencing data from New Guinean samples originated from the 22 provinces of Papua New Guinea, and from West Papua (Indonesia). Analyses used an exhaustive comparative dataset, SNP frequency-based (e.g., f3 and f4-statistics) and haplotype-based approaches (FineSTRUCTURE, GLOBETROTTER), and a large interpretative framework (archaeology, anthropology, linguistic). This allows to propose a better description of the different phases of human settlement in New Guinea Island, and better understand the current anthropological landscape.