Abstract: Background and Objective: Nowadays, sulfonylurea including Glipizide have been tested to manage diabetes. However, their safety index yet not extensively studied. Our research aims were to assess neuro and the major organs' safety of Glipizide while their effects on different lipid and other biomedical parameters have been also tested. Materials and Methods: Streptozotocin (STZ)-induced T2DM in male swiss Albino mice model has been developed on twenty rats and assigned to four different groups to receive their treatments. At the end of 7 days treatment protocol, the neurological study was carried out by open field, hole board, forced swimming, dark and lighthouse and elevated plus-maze test. After sacrifice, major organs weight and serum level of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), total cholesterol (TC) and triglyceride (TG) have been evaluated. Results: Glipizide produces some neurological effects in almost all laboratories set up except elevated plus-maze test, whereas an effect on the whole board test was found better than standard diazepam. Present data replicate the significant downflow for plasma glucose and body weight gain over the treatment period while also having minimal effect on major organ weight and fat deposition. It also exposed that Glipizide also has some suppressing effects on TC, TG, LDL-C, VLDL-C levels compared to the control group. Conclusion: Present findings bring a clear projection that Glipizide at a dose of 5 mg kg–1 generates some anxiolytic activity with a remarkable plasma, glucose level and bodyweight reduction and minimal effects on lipid profile and major organs weight variation.