Background Analysis of the correlation between diabetes type 2 (DT2) and serum N-acetyl-β-hexosaminidase (HEX) activity with parameters of fat metabolism and symptoms of anxiety and depression. Material and Method The study was performed using a random sample of 40 DT2 patients (22 women and 18 men) between the ages of 43 and 71 (median 59) and 40 control persons (28 women and 12 men) between the ages of 18 and 64 (median 46). The activity of HEX was determined by a colorimetric method. The activity of the serum exoglycosidase was expressed in pkat/mL. Each participant underwent Hamilton tests, to evaluate level of anxiety and depression. Additionally, the HEX activity and concentration of particular lipidograms were monitored using a blood sample from each participant. Results In DT2 patients, a significant positive correlation was found between serum HEX activity and the concentration of serum cholesterol LDL fractions, triacylglycerols (TAG), and Castelligro atherogenic indexes. A significantly increased level of anxiety and depression in comparison to the control group was found as well. Conclusion Serum HEX activity in DT2 patients is a better marker of atherosclerosis than serum total cholesterol level in persons with mild symptoms of depression and anxiety. In DT2 patients, a routine testing of anxiety and depression is recommended. Early detection of these disorders creates the possibility for treatment, an improvement in a patient's quality of life, and the overall longevity of DT2 patients.