|Optical waveguide sensors based on gratings and metamaterials for refractive index (RI) sensing are introduced in this Ph.D. dissertation. A waveguide is a structure which can guide light based on total internal reflection. When a waveguide is applied as an optical sensor, it uses different forms of light–matter interactions to measure or quantify molecules, and be used in biological and chemical applications. A diffraction grating is an optical element with a periodic structure which diffracts incident light into several beam in different directions based on the properties of the light. Metamaterials are engineered materials designed to have properties that do not occur naturally. In this work, gratings are applied to interact with incident light and to produce changes in the phase and amplitude of the output light. When it is combined with a waveguide, a diffraction grating coupled waveguide based biosensor can be designed. When the light is input with an angle to the biosensor, the grating not only diffracts the light, but allows the light to effectively couple with the waveguide thus providing interaction with the analyte of interest. A Bragg gratings waveguide (BGW) is a waveguide with periodic structures of RI along the waveguide core. When the light is incident normal to the BGW, the light will be confined to generate a resonance. Two waveguide biosensors based on Bragg gratings are designed. The double sided Bragg gratings waveguide (DSBGW) based biosensor uses Bragg gratings in silicon on insulator (SOI) wafer to measure the target analyte. The light will interact with the gratings and the analyte surrounding the waveguide, and the change of RI of analyte will lead to a change in the resonance peak of the spectrum. Compared with DSBGW, when the waveguide is also coupled with a slot, the double sided Bragg gratings in slot waveguide (DSBGISW) based biosensor is designed and can achieve better performance. Metal gratings when patterned appropriately can act as a metamaterial. When a liquid-core waveguide and gold/dielectric metamaterial are integrated in the biosensor design, it produces resonance in the waveguide when the light interacts with the metamaterial structure in the core. The sensor is able to detect a liquid analyte by converting the change in the RI of the analyte to a shift of resonance peak in the output spectrum. The different light guiding properties of the structure will determine the peaks in the spectrum and enhance the sensitivity. A metamaterial based biosensor has been characterized through simulation and experimentation.