Most elderly patients after orthopedic and dental implant surgeries are exposed to cardiostimulants to reduce potential blood pressure-related risks of cardiovascular diseases. Such treatments lead to deconditioning of platelet function, which is an important factor in wound healing treatments. We introduced an innovative parylene-C coated microporous PDMS structure that can prevent the functional deconditioning of platelets caused by certain cardiostimulants. At different concentrations of cardiostimulants (IPR; isoprenaline and DA; dopamine), pre-activation, activation, and post-activation of platelets were intensively examined under mechanical and chemical stimulation mimicking the physiological environment on four different surfaces (glass, flat parylene-C coated glass (F-PPXC), microporous PDMS structure (P-PDMS), and parylene-C-coated microporous PDMS structure (S-PPXC)). The 3D microporous structure with parylene-C (S-PPXC) surface could attenuate the deconditioning of platelet function caused by IPR. Moreover, the S-PPXC surface further enhanced the DA-dependent stimulation of platelet function. The reason for this is that the 3D microporous structure with parylene-C S-PPXC induced stable and fast adhesion of platelets through increased surface roughness and softness, resulting in a significant enhancement of platelet activity. Therefore, we propose the use of functional S-PPXC surfaces as a novel strategy in the development of biomedical products.