Background: Type-2 diabetes mellitus (T2DM) is associated with various chronic diseases, neurocognitive disorders, and vascular encephalopathy. Objectives: screening of T2DM patients for the control of blood glucose (BG), the presence of manifestations of altered mood and/or cognitive impairment (CI), and dysregulated serum levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 and IL1β. Patients and methods: 225 T2DM patients underwent estimation of fasting (FBG) and 2-h postprandial BG (PPBG), glycosylated hemoglobin A1c (HbA1c) and the homeostasis model assessment of insulin resistance (HOMA-IR) score. The presence and severity of depression and anxiety were assessed using the Hospital Anxiety and Depression Scale (HADS). Mini-Mental State Examination (MMSE) and the Cognitive Change Index (CCI) were used to evaluate cognitive impairment (CI) and memory performance. Blood samples were obtained for ELISA estimation of serum cytokines' levels. Study outcome is the interrelation between the glycemic and psychological statuses and cytokines' levels.   Results: Sixteen and 56 patients showed manifest anxiety and depression, respectively while 155 patients had CI. Serum cytokines' levels showed positive correlation with PPBG, HOMA-IR and HbA1c%, and with HADS and CCI scores, while showing negative correlation with MMSE score. Regression analysis defined TNF-α as significant (P<0.001) predictor for high HADS-D and low MMSE scores (P<0.001), while PPBG levels were the significant (P<0.001) predictors for high HADS-A and high IL-1β (P<0.001) for high CCI. Conclusion: Uncontrolled DM deleteriously impacted patients' psychological status, memory, and cognitive functions. High levels of serum TNF-α, PPBG, and HOMA-IR might predict impaired psychological status and memory function.