Background/objectives Obesity and periodontitis are systemic subclinical inflammatory diseases with established negative renal effects. The aim of this animal study was to thoroughly investigate the possible effects of these two diseases on renal structure and function. Methods Thirty-two male Sprague Dawley rats were divided into four groups: control (C), obesity (Ob), experimental periodontitis (Ep), and Ob + Ep. The first 16 weeks of the experiment were aimed for the induction of obesity and the last 5 weeks for the induction of periodontitis. Throughout the experimental period, the C and Ep groups were fed standard rat chow, while the Ob groups (Ob and Ob + Ep) were fed high-fat rat chow. Right after the establishment of obesity, periodontal tissue destruction was achieved by placing 3.0 silk sutures in sub-paramarginal position around the cervices of mandibular right-left first molar teeth and preserving them for 5 weeks. On the last day of the 22(nd) week, following blood collection, all rats were euthanized, and kidneys and mandibles were collected. Alveolar bone loss was measured on microcomputed tomographic slices. Histopathological evaluations (light microscopy, semi-quantitative analysis of renal corpuscle area, and immunohistochemical analysis of caspase-3 activity) were done on right kidneys and biochemical evaluations (malonyl-aldehyde [MDA], glutathione [GSH], total oxidant status [TOS], total antioxidant status [TAS], oxidative stress [OSI], tumor necrosis factor-alpha [TNF-alpha], interleukin-1 beta [IL-1 beta], matrix metalloproteinase [MMP]-8, MMP-9, and cathepsin D [CtD] levels) were done on left kidneys. Renal functional status was evaluated with levels of serum creatinine, urea, and cystatin C. Results Periodontal bone loss was significantly higher in the Ep and Ob + Ep groups, compared with the C and Ob groups (p < .05). All parameters except TAS and GSH were highest in the Ob + Ep group, and the differences were statistically significant compared with the control group (p < .05). Although the mean TAS and GSH levels were lower in the Ob + Ep group than the other groups, the differences were not statistically significant (p > .05). While the atypical glomeruli score was significantly higher in the Ob + Ep group than in all other groups (p < .05), the acute tubular necrosis and histopathological scores were significantly different only compared with the control group (p < .05). Conclusion This experimental study showed that the negative effects of the co-existence of periodontitis and obesity on inflammatory stress and apoptotic changes in the kidneys together with the functional parameters were significantly more severe, compared with the presence of one of these diseases alone. TNF-alpha could have a central role in the periodontitis and obesity-related structural and functional renal changes.