Alpelisib, a phosphatidylinositol-3-kinase (PI3K) inhibitor, is a new drug approved for metastatic breast cancer. Hyperglycemia is a known side effect of this medication, however diabetic ketoacidosis is rarely described. We are presenting a 64-year-old female with a known case of Type 2 diabetes mellitus (hemoglobin A1c [HbA1c] 5.6% ) controlled by metformin alone. She was also diagnosed with metastatic breast cancer. She received radiotherapy, trastuzumab and letrozole. Then, she was started on alpelisib as she failed other previous modalities. She presented to the emergency department with a two-week history of polyuria and polydipsia, and laboratory investigation results showed high anion gap metabolic acidosis, ketonemia, and hyperglycemia. She was treated for diabetic ketoacidosis (DKA). After the resolution of DKA, she was kept on daily insulin subcutaneous injections. She was restarted on a reduced dose of alpelisib, but despite this, her blood sugar readings continued to rise, requiring discontinuation of the medication with a resolution of hyperglycemia. The goal of our case report is to emphasize the importance of close glucose monitoring when starting alpelisib to avoid serious complications like DKA.