Integrating novel materials is critical for the ultrasensitive, multi-dimensional detection of biomolecules in the terahertz (THz) range. Few studies on THz biosensors have used semiconductive active layers with tunable energy band structures. In this study, we demonstrate three THz biosensors for detecting casein molecules based on the hybridization of the metasurface with graphitic carbon nitride, graphene, and heterojunction. We achieved low-concentration detection of casein molecules with a 3.54 ng/mL limit and multi-dimensional sensing by observing three degrees of variations (frequency shift, transmission difference, and phase difference). The favorable effect of casein on the conductivity of the semiconductive active layer can be used to explain the internal sensing mechanism. The incorporation of protein molecules changes the carrier concentration on the surface of the semiconductor active layer via the electrostatic doping effect as the concentration of positively charged casein grows, which alters the energy band structure and the conductivity of the active layer. The measured results indicate that any casein concentration can be distinguished directly by observing variations in resonance frequency, transmission value, and phase difference. With the heterojunction, the biosensor showed the highest response to the protein among the three biosensors. The Silvaco Atlas package was used to simulate the three samples’ energy band structure and carrier transport to demonstrate the benefits of the heterojunction for the sensor. The simulation results validated our proposed theoretical mechanism model. Our proposed biosensors could provide a novel approach for THz metasurface-based ultrasensitive biosensing technologies.