The design criteria of integrated optical biosensors based on the Mach-Zehnder Interferometer and on the Michelson Interferometer are proposed. Sensitive performance has been evaluated for different optical polymeric waveguiding structures such as channel, inverted-rib and strip waveguides. For all the configurations of the examined optical waveguiding interferometric biosensors maximum linearity and sensitivity have been obtained. In particular, the achieved sensitivity, expressed as the ratio between the normalized output power and the protein concentration, is about equal to 1.6 (g/ml) −1 which, for a maximum variation of the output power equal to 100 mW, leads to a non-normalized sensitivity equal to 160 mW/(g/ml).