Background: Several studies have demonstrated an association between obesity, periodontitis, and exercise. Aims: This study aimed to investigate the effects of regular exercise on obese women with periodontal disease, using serum, saliva, and gingival crevicular fluid (GCF) samples. A before-after study design was adopted to evaluate the effects of 12 weeks of regular exercise on obese women grouped according to periodontal status, without a control group (no exercise). The study sample comprised of 15 patients without periodontitis (NP group) and 10 patients with chronic periodontitis (CP group), from whom periodontal parameters were measured and serum, saliva, and GCF samples were collected. Body mass index (BMI), anthropometric measurements, somatotype-motoric tests, and maximal oxygen consumption (VO2max) were recorded at baseline and after exercise. Subjects and Methods: Med Calc was used for statistical analysis. Results: After exercise, a significant decrease in BMI and a significant increase in VO2max were observed in both groups. A significant decrease in probing depth and clinical attachment loss, serum leptin, GCF tumor necrosis factor-alpha(TNF-alpha) and leptin, and a significant increase in GCF resistin were observed in the CP group. A significant decrease in serum TNF-alpha and leptin levels and a significant increase in serum resistin and GCF TNF-alpha, leptin, resistin, and adiponectin levels were observed in the NP group. Significant correlations between bleeding on probing and levels of interleukin-1 beta and leptin in GCF were observed in the CP group. Conclusions: This study showed that regular exercise exerts different impacts with respect to clinical and biochemical aspects of periodontal and systemic conditions in obese women.