A simple, sensitive, and efficient method has been developed for simultaneous estimation of valsartan and atorvastatin in human plasma by combination of solid-based dispersive liquid–liquid microextraction and high performance liquid chromatography–diode array detection. In the proposed method, 1,2-dibromoethane (extraction solvent) is added on a sugar cube (as a solid disperser) and it is introduced into plasma sample containing the analytes. After manual shaking and centrifugation, the resultant sedimented phase is subjected to back extraction into a small volume of sodium hydrogen carbonate solution using air-assisted liquid–liquid microextraction. Then the cloudy solution is centrifuged and the obtained aqueous phase is transferred into a microtube and analyzed by the separation system. Under the optimal conditions, extraction recoveries are obtained in the range of 81–90%. Calibration curves plotted in drug-free plasma sample are linear in the ranges of 5–5000 μg L−1 for valsartan and 10–5000 μg L−1 for atorvastatin with the coefficients of determination higher than 0.997. Limits of detection and quantification of the studied analytes in plasma sample are 0.30–2.6 and 1.0–8.2 μg L−1, respectively. Intra-day (n = 6) and inter-days (n = 4) precisions of the method are satisfactory with relative standard deviations less than 7.4% (at three levels of 10, 500, and 2000 μg L−1, each analyte). These data suggest that the method can be successfully applied to determine trace amounts of valsartan and atorvastatin in human plasma samples.