To improve the electrode-nerve interface of cochlear implants (CI), the role of poly(L-lactide) (PLLA) and poly(4-hydroxybutyrate) (P(4HB)) as potential coating matrices for CI was assessed both in vitro and in vivo in terms of degradation behavior and effects on spiral ganglion neurons, the main target of the electrical stimulation with a CI. Growth rates of fibroblasts on the polymers were investigated and a direct-contact test with freshly isolated spiral ganglion cells (SGC) was performed. In addition, the effects of the polymer degradation inside the inner ear were evaluated in vivo. The polymer degradation was assessed by use of scanning electron microscopy in combination with an energy-dispersive X-ray analysis. In vitro, no influence of the polymers was detected on fibroblasts' viability and on SGC survival rate. In vivo, SGC density was decreased only 6 months after implantation in the basal and middle turns of the cochlea in comparison to normal-hearing animals but not between implanted groups (coated or uncoated). The analysis of the electrode models showed that in vivo P(4HB) is characterized by a gradual degradation completed after 6 months; whereas, the PLLA coatings burst along their longitudinal axis but showed only little degradation within the same time frame. In conclusion, both polymers seem to justify further evaluation as possible coating for CI electrodes. Of the two options, due to its excellent coating adhesion/stability and optimal degradation behavior, P(4HB) may prove to be the more promising biodegradable polymer for designing a drug delivery system from the surface of CI electrodes.