Objectives: To evaluate the effect of atypical antipsychotics on serum glucose levels and HbA1C in patients of schizophrenia and bipolar disorder. Study Design: Quasi-experimental study. Setting: Department of Neurology and Sir C. J Institute of Psychiatry LUMHS Jamshoro/Hyderabad. Period: Dec 2018-Dec 2019. Material & Methods: Total 360 participants of age more than 15 years of either gender presenting with psychiatric illness i.e. schizophrenia and bipolar disorder and prescribed same brand of antipsychotic drugs were included in the study. Fasting blood glucose (FBS), random blood glucose (RBS) and glycosylated hemoglobin (HbA1c) were measured at baseline and 6th months after treatment with atypical antipsychotic agents. SPSS version 23 was used to analyze data. Results: A total of 360 patients were enrolled in the study duration, among them 338 patients were followed up till 6 months, while 22 patients were lost to follow up. The mean age of the study sample was reported as 39.33±8.83 years. At baseline mean FBS, RBS and HbA1c were reported as 92.52±9 mg/dl, 143.21±14.91, 5.83±0.37 which significantly increase after treatment with antipsychotics at 6 months (p<0.05). About 23.6% developed diabetes mellitus and 21.3% developed hyperglycemia at the end of 6 months. Conclusion: Non-diabetic treatment naïve schizophrenia and bipolar disorders patients have higher chances developing side-effects on the glucose regulations after initiation of antipsychotic therapy. Overall, the early identification and diagnosis of antipsychotic-induced diabetes mellitus and hyperglycemia requires proper evaluation, reporting, and physician and patient awareness.