Optical fiber biosensors (OFBS) are being increasingly proposed due to their intrinsic advantages over conventional sensors, including their compactness, potential remote control and immunity to electromagnetic interference. This review systematically introduces the advances of OFBS based on long-period fiber gratings (LPFGs) for chemical and biomedical applications from the perspective of design and functionalization. The sensitivity of such a sensor can be enhanced by designing the device working at or near the dispersion turning point, or working around the mode transition, or their combination. In addition, several common functionalization methods are summarized in detail, such as the covalent immobilization of 3-aminopropyltriethoxysilane (APTES) silanization and graphene oxide (GO) functionalization, and the noncovalent immobilization of the layer-by-layer assembly method. Moreover, reflective LPFG-based sensors with different configurations have also been introduced. This work aims to provide a comprehensive understanding of LPFG-based biosensors and to suggest some future directions for exploration.