Objective Regulators of peri???implant bone loss in patients with diabetes appear to involve multiple risk factors that have not been clearly elucidated. This study was conducted to explore putative local etiologic factors on implant bone loss in relation to type 2 diabetes mellitus, including clinical, microbial, salivary biomarker, and psychosocial factors. Materials and methods Thirty???two subjects (divided into type 2 diabetes mellitus and non???diabetic controls), having at least one functional implant and six teeth, were enrolled in a 1???year longitudinal investigation. Analyses of clinical measurements and standardized intra???oral radiographs, saliva and serum biomarkers (via protein arrays for 20 selected markers), and plaque biofilm (via q PCR for eight periodontal pathogens) were performed at baseline and 1??year. In addition, the subjects were asked to respond to questionnaires to assess behavioral and psychosocial variables. Results There was a significant increase from baseline to 1??year in the probing depth of implants in the diabetes group (1.95??mm to 2.35??mm, P ??=??0.015). The average radiographic bone loss during the study period marginally increased at dental implants compared to natural teeth over the study period (0.08??mm vs. 0.05??mm; P ??=??0.043). The control group harbored higher levels of T reponema denticola at their teeth at baseline ( P ??=??0.046), and the levels of the pathogen increased significantly over time around the implants of the same group ( P ??=??0.003). Salivary osteoprotegerin ( OPG ) levels were higher in the diabetes group than the control group at baseline only; in addition, the salivary levels of IL ???4, IL ???10, and OPG associated with host defense were significantly reduced in the diabetes group ( P ??=??0.010, P ??=??0.019, and P ??=??0.024), while controls showed an increase in the salivary OPG levels ( P ??=??0.005). For psychosocial factors, there were not many significant changes over the observation period, except for some findings related to coping behaviors at baseline. Conclusions The study suggests that the clinical, microbiological, salivary biomarker, and psychosocial profiles of dental implant patients with type 2 diabetes who are under good metabolic control and regular maintenance care are very similar to those of non???diabetic individuals. Future studies are warranted to validate the findings in longer???term and larger clinical trials ( ClinicalTrials.gov # NCT00933491).