The health of humans is intricately linked to the substances we ingest—both food and nondietary items. Adverse health outcomes related to smoking of such products as tobacco and other psychoactive substances are clearly established in modern populations but are less well understood for ancient communities. Grasping these dynamics is further complicated by the curative, religious, and medicinal context of many of these substances, which have often been commodified, refined, and altered in recent history. As part of a larger collaboration with the Muwekma Ohlone Tribe dedicated to understanding medicinal plant use among Native Californians, this article summarizes new metabolomic data from three Middle- and Late-Period ancestral heritage Ohlone sites: Thámien Rúmmeytak (CA-SCL-128),'Ayttakiš'Éete Hiramwiš Trépam-tak (CA-ALA-677/H), and Síi Túupentak (CA-ALA-565/H). The authors used an ultra-performance liquid chromatography-mass spectrometry platform to analyze chemical residues from 95 human dental calculus samples from 50 burials. Using multivariate statistics, they coanalyzed demographic and skeletal pathology data with chemical residue profiles and considered skeletal markers for a series of oral and postcranial health conditions. Results indicate sex and age biases in consumption patterns. Periodontitis stands out as the most significant local factor for changes in the oral metabolome. However, while chemical markers of oral diseases may be related to pathogen activity, associations between residues and postcranial conditions such as osteoarthritis suggest traditional curative practices and the ingestion of medicinal substances. Hence, this study yields new insights into the broader context of illness and healing in the past.