An evanescent-field-coupled waveguide-mode sensor with a multilayer structure consisting of a dielectric waveguide, a thin reflecting layer, and a glass substrate illuminated under the Kretschmann configuration operates as a sensor that is capable of detecting modifications in the dielectric environment near the waveguide surface with superior sensitivity by measuring the change in reflectivity. The sensitivity of the sensor is strongly dependent on the optical constants of the reflecting layer. Numerical simulations show that a sensor having a reflecting layer with a small value of the real part of the complex refractive index shows a good sensitivity for both S- and P-polarized light. Materials with values of the real and imaginary parts of the complex refractive index of >4 and ∼0.5, respectively, are suitable for use as reflecting layers when S-polarized light excites only the lowest order waveguide mode. The simulations were experimentally confirmed using sensors with Au, Cu, Cr, W, a-Si, or Ge reflecting layers deposited by radiofrequency magnetron sputtering by observation of specific adsorption of streptavidin on biotinyl groups using an S-polarized laser beam with a wavelength of 632.8 nm. From the results, guidelines are given for the fabrication of preferred sensor configurations.