Antioxidant capacity is frequently measured by evaluating superoxide dismutase (SOD) concentration in body fluids. The aim of this study was to compare SOD concentrations in the saliva and plasma of patients with periodontitis to those measured in a group of patients with healthy periodontium, as well as to evaluate the influence of nonsurgical periodontal therapy on salivary and plasma SOD in periodontitis patients. For this purpose, 40 systemically healthy patients aged 30–70 years who had at least 20 teeth were recruited, 20 of whom had periodontitis, and 20 served as healthy periodontitis-free controls. In all participants, periodontal status was assessed via the plaque index (PI), gingival index (GI), papilla bleeding index (PIB), probing depth (PD), and clinical attachment level (CAL), and the SOD concentration in both saliva and plasma was determined by conducting a commercial immunoenzymatic ELISA test. In periodontitis patients, periodontal indices and saliva and blood samples were taken at the beginning of the study, as well as 3 months after periodontal therapy, while in the control group, these data were gathered at the beginning of the study only. SOD values in the saliva of patients with periodontitis (0.244 U/µL) were statistically significantly higher compared with patients with healthy periodontium (0.017 U/µL). Moreover, periodontal therapy led to a statistically significant decrease in this marker in the saliva of patients with periodontitis (p = 0.023), which was comparable with that measured in the control group. On the other hand, no statistically significant differences were noted in plasma SOD values either between the two groups or at follow-up compared with baseline in the group with periodontitis. These findings suggest that the elevated salivary SOD in patients with periodontal disease may represent a mechanism of tissue protection against oxidative stress that occurs in response to periodontal disease.