Objectives The south coast of New Guinea has a complex prehistory known for its exchange systems that linked distinct cultural groups living along the coast, inland, and on offshore islands. Here we compare the palaeohealth of two relatively contemporaneous skeletal samples from the south coast of New Guinea (850–200 BP) that were from two ecologically different sites (one inland and one offshore island) and likely represent distinct cultural groups. We aim to elucidate health patterns that may provide information about the specific lifeways and quality of life of each community. Materials and Methods Oral conditions (caries, calculus, alveolar lesions, and antemortem tooth loss [AMTL]) were analyzed macroscopically to assess possible intra‐ and inter‐population variation in oral and physiological health. The frequency of linear enamel hypoplasia (LEH) was also used as a nonspecific indicator of stress to assess childhood health at each site. Results The inhabitants from the small offshore island of Motupore, thought to be associated with Austronesian‐speaking Motu tribes, displayed different patterns of oral pathological conditions (more carious lesions on the tooth crown and calculus) and LEH (lower frequencies) compared with inland people residing at the site of Nebira. Discussion It is suggested that the causes for the variation in oral and physiological health were likely multifactorial and potentially associated with variables such as the ecological and geographical settings of the sites, cultural differences, infectious disease, differential fertility and, potentially, diet. This research provides previously unknown information about possible culturally‐moderated practices that affected health in the past. Am J Phys Anthropol 160:414–426, 2016. © 2016 Wiley Periodicals, Inc.