Cardiovascular disease (CVD) remains the leading cause of death worldwide, with underlying mechanisms often involving platelet activation and chronic inflammation. While antiplatelet agents targeting adenosine diphosphate (ADP)-mediated pathways are well established in CVD management, less is known about their effects on the platelet-activating factor (PAF) pathway—a key mediator of inflammation and thrombosis. This study evaluates the antiplatelet and anti-inflammatory profiles of several commonly used cardiovascular and anti-inflammatory drugs through dual-pathway assessment of ADP- and PAF-induced platelet aggregation. Using human platelet-rich plasma (hPRP) from healthy donors, we assessed platelet responses in the presence of clopidogrel and a range of non-steroidal anti-inflammatory drugs (NSAIDs), including lornoxicam, diclofenac, ketoprofen, naproxen, etoricoxib, niflumic acid, allopurinol, and nimesulide. Clopidogrel confirmed its well-established ADP antagonism and also demonstrated inhibitory activity against the PAF pathway, suggesting a broader and underrecognized pharmacodynamic profile. Notably, several NSAIDs—particularly lornoxicam and diclofenac—exhibited strong inhibitory effects on both platelet activation pathways, whereas naproxen showed comparatively weak activity. These results emphasize the potential for pathway-specific pharmacological action among NSAIDs. Our findings highlight the value of evaluating drug effects beyond their conventional targets. By considering both PAF- and ADP-mediated mechanisms, this dual-pathway analysis contributes to a more nuanced understanding of drug function. Such insights may support the development of more comprehensive and personalized therapeutic strategies for cardiovascular, hypertensive, and inflammation-driven diseases.