This manuscript reports an experimental study on surfaces of natural rubber membranes modified by incorporation of calcium phosphate particles. In particular, we focused on the wettability, a subject for biological aspects. Five surfaces of natural rubber (NR) membranes (pure, polymer-bioceramic composite (NR-CaP), and three modified surfaces subjected to a simulated body fluid (NR-SBF)) were produced and characterized by confocal Raman-spectroscopy, AFM, SEM, and XPS, and the results were correlated with the wetting properties. Seven liquids (water, formamide, di-iodomethane, ethylene glycol, hexadecane, simulated body fluid, and human blood droplets) were used in different experimental sections. Static and dynamic contact angle measurements were conducted to obtain the solid–liquid tensions, work of adhesion, and depinning forces. The incorporation of CaP particles in the polymer decreases the roughness and increases the interfacial adhesion, and there was no dependence between the morphology and equilibrium contact line. The hydrophobic state of the NR surfaces is preserved. After exposure to a biological environment, the NR surfaces were chemically modified increasing blood wettability and decreasing the negative surface charges and the contact angle to values close to those associated with protein adsorption and cell adhesion, therefore opening possibilities for applications of these materials as biomembranes. On the other hand, the concepts applied, regarding different wettability aspects, should enable the evaluation of biomaterial surfaces and provide new insights allowing a better understanding of body fluid–material interfaces.