This paper investigates the effects of annealing of the electrodes based on parylene-caulked polydimethylsiloxane (pc-PDMS) in terms of mechanical strength and long-term electrical property. Previously, the electrodes based on pc-PDMS showed a better ability to withstand in vivo environments because of the low water absorption and beneficial mechanical properties of the substrate, compared to native PDMS. Moreover, annealing is expected to even strengthen the mechanical strength and lower the water absorption of the pc-PDMS substrate. To characterize the mechanical strength and water absorption of the annealed pc-PDMS, tensile tests were carried out and infrared (IR) spectra were measured using Fourier transform infrared spectroscopy over a month. The results showed that annealed pc-PDMS had higher mechanical strength and lower water absorption than non-annealed pc-PDMS. Then, electrochemical impedance spectroscopy was measured to evaluate the electrical stability of the electrodes based on annealed pc-PDMS in phosphate-buffered saline solution at 36.5 °C. The impedance magnitude of the electrodes on annealed pc-PDMS was twice higher than that of the electrodes on non-annealed pc-PDMS in the initial days, but the impedance magnitude of the electrodes based on two different substrates converged to a similar value after eight months, indicating that the annealing effects disappear after a certain period of time in a physiological environment.