Green, simple and accurate micellar UPLC method was established and validated for quantitative determination of glimepiride, pioglitazone HCl, Valsartan and atorvastatin calcium trihydrate in bulk powder, tablets and spiked human plasma. Gradient separation was achieved on Kinetex 1.7µ C18 100A (2.1-mm × 50-mm) at ambient temperature using ecofriendly gradient mobile phase composed of a mixture of 0.05 M potassium dihydrogen phosphate buffer pH 5.00 (A) with 0.10M sodium dodecyl sulfate and isopropanol (15.00-25.00%) (B) at flow rate of 0.20 mL/minute and UV detection at 230.00 nm using metformin as internal standard. The method was linear in the range of 0.50–25.00 μg/mL. The proposed method was effectively applied for the determination of glimepiride, pioglitazone HCl, valsartan and atorvastatin in bulk powder, pharmaceutical dosage forms and human plasma with good accuracy and precision. The results were compared with those of the reported methods and were found to be in good agreement. The proposed method was validated according to ICH guidelines.