Fiber-optic biosensors have the capability of detecting chemical or biological substance relying on the interaction of the evanescent wave to the surrounding, which probe the light signal change as a result of the specific binding of the biological recognition molecule and the target molecule. With the advantages such as small size and flexibility, fiber-optic sensors are promising to serve as an advanced methodology for in-situ bio/chemical detection. In particular, the microfiber interferometric biosensor with the microfiber modal interferometer as the energy converter can achieve ultra-high sensitivity for biomolecule detection even down to the level of single-molecule, through signal amplification by optimizing the optical waveguide structure and the interface. This review introduces the microfiber modal interferometer in terms of the principle, preparation, sensitivity characteristics, biosensor implementation and interface sensitivity enhancement.