Background Oral anti-platelet agents are the cornerstone of the treatment of multiple cardiovascular diseases and in the long-term prevention of their recurrence. Objective In the present work, we report a method based on micellar liquid chromatography coupled with ultraviolet detection (MLC/UV), for the simultaneous quantification of combined anti-platelet therapy namely, clopidogrel bisulfate (CPS), aspirin (ASP), together with salicylic acid (SA), in their pharmaceutical dosage form. Methods The incorporation of 0.1M polyoxyethylene 23 lauryl ether (Brij-35) as a surfactant into the mobile phase improved solute–mobile phase interaction allowing for minimal organic solvent utilization, enhanced resolution, and rapid analysis (7 min). Furthermore, we performed a comprehensive evaluation of the environmental impact caused by our procedures versus previously reported analytical procedures applied in the determination of CPS and ASP. The evaluation was made using the Eco-scale tool. Results The results of the developed method indicated the superiority of our procedures in terms of greenness without compromising the quality of performance characteristics. The method was linear in the range of 1–100 µg/mL with limits of detection of 0.28, 0.32, and 0.29 µg/mL for CPS, ASP, and SA, respectively. The developed method can also be utilized to test the purity and the stability of ASP in pharmaceutical formulations through monitoring SA as its main degradation product. Conclusion The MLC/UV method was successfully applied to the quantitative analysis of CPS, ASP together with SA—as a main degradation product of ASP—in their pharmaceutical dosage form