Purpose In some diabetic patients receiving omalizumab therapy, blood glucose regulation is impaired. However, the effect of omalizumab on glucose homeostasis in non-diabetic patients remains unknown. Methods The patients were given subcutaneous omalizumab at a dose of 300 mg every four weeks for the treatment of chronic urticaria in this study. Fasting blood glucose, fasting plasma insulin, total cholesterol, triglyceride, and high-density (HDL) and low-density lipoprotein (LDL) were studied before and at the 12th week of treatment. The homeostatic model assessment for insulin resistance (HOMA-IR) was used to determine insulin resistance. Results Forty of the 45 patients included in the study completed 12 weeks of treatment. While fasting blood glucoses (p = 0.011) and HOMA-IR values (p = 0.027) were significantly increased in the 12th week, the increase in fasting insulin level was not significant (p = 0.07). After treatment, 10 patients developed impaired fasting glucose and 13 developed insulin resistance. Conclusion The increase in blood glucose levels may be associated with the paradoxically increase of histamine levels in the blood by omalizumab. If this increase cannot be balanced with insulin, patients may develop impaired glucose tolerance and insulin resistance. Therefore, we suggest that patients using omalizumab should be followed up for glucose homeostasis and insulin resistance.