Objective. This study investigates the association of homocysteine and cortisol with psychological factors in type 2 diabetic patients. Method. Homocysteine, cortisol, and psychological variables were analyzed from 131 diabetic patients. Psychological factors were assessed with the Eysenck Personality Questionnaire (EPQ), Hostility and Direction of Hostility Questionnaire (HDHQ), the Symptom Checklist 90-R (SCL 90-R), the Zung Self-Rating Depression Scale (ZDRS), and the Maudsley O-C Inventory Questionnaire (MOCI). Blood samples were taken by measuring homocysteine and cortisol in both subgroups during the initial phase of the study (T0). One year later (T1), the uncontrolled diabetic patients were reevaluated with the use of the same psychometric instruments and with an identical blood analysis. Results. The relation of psychoticism and homocysteine is positive among controlled diabetic patients (P value = 0.006<0.05) and negative among uncontrolled ones (P value = 0.137). Higher values of cortisol correspond to lower scores on extraversion subscale (rp=-0.223, P value = 0.010). Controlled diabetic patients showed a statistically significant negative relationship between homocysteine and the act-out hostility subscale (rsp=-0.247, P=0.023). There is a statistically significant relationship between homocysteine and somatization (rsp=-0.220, P=0.043). Conclusions. These findings support the notion that homocysteine and cortisol are related to trait and state psychological factors in patients with diabetes mellitus type 2.