The principle purpose of the present study was to investigate in vitro complex formation and to study the nature and strength of complexes which could be formed due to interaction of Metformin or Pioglitazone with Naproxen and Ibuprofen. Metformin and Pioglitazone are anti-diabetic drugs; Metformin is the first-line drug of choice for the treatment of type 2 diabetes, particularly in overweight and obese people and those with normal kidney function. Pioglitazone is an anti-diabetic drug (thiazolidinedione-type, also called "glitazones") used along with a proper diet and exercise program to control high blood sugar in patients with type 2 diabetes (noninsulin- dependent diabetes). It works by helping to restore your body's proper response to insulin, thereby lowering your blood sugar. On the other side, Naproxen and Ibuprofen, both are NSAIDs, commonly used for the reduction of pain, fever, inflammation and stiffness caused by conditions such as osteoarthritis, kidney stones, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, menstrual cramps, tendinitis, bursitis, and the treatment of primary dysmenorrhea. It works by inhibiting both the COX-1 and COX-2 enzyme