Glutamate excitotoxicity and oxidative stress are held responsible for the pathogenesis of Alzheimer's disease (AD). Prolidase is known to have a crucial part in the recycling of proline for collagen synthesis. Elevated proline levels have been shown to increase glutamate concentration. To our knowledge, prolidase activity in AD has not yet been studied. In this study, we aimed to reveal the relationship of AD with oxidative stress and collagen turnover by comparing AD patients and healthy control group with regard to total antioxidant status (TAS), total oxidant status (TOS), and prolidase levels. Fifty patients (mean age, 72.5 ± 8.9 years) diagnosed with AD and a control group comprised of 39 healthy individuals (mean age, 69.1 ± 7.1 years) were compared relative to serum TAS, TOS, and prolidase levels. The relationship of cognitive performance with prolidase, TAS, and TOS was evaluated by Mini mental state examination (MMSE). Alzheimer's disease group demonstrated statistically significantly higher prolidase and TOS levels as compared to the control group (p = 0.01, p = 0.018, respectively). Total antioxidant status level was significantly lower in the dementia group than in the control group (p = 0.032). MMSE manifested a negative correlation with prolidase and TOS levels (p = 0.001, r = -0.33; p = 0.002, r = -0.32, respectively), while displaying a positive correlation with TAS levels (p = 0.002, r = 0.32). In conclusion, elevated prolidase and TOS levels along with reduced TAS concentrations suggest that oxidative stress and collagen breakdown are involved in the cognitive impairment in AD.