New types of metal–organic framework (MOF) materials have great potential in solving the current global dilemma on energy, environment, and medical care. Herein, based on two kinds of biomolecule-MOFs (Bio-MOFs) with favorable biocompatibility and degradation-reconstruction characteristics, we have established a self-powered muti-functional device to achieve an efficient and broad-spectrum environmental energy collection and biomedical applications. Combining Zn(II) and carnosine-based Zn-Car_MOF possessing a high piezoelectric response (d33 = 11.17 pm V−1) with patterned polydimethylsiloxane (PDMS) film, a tribo-piezoelectric hybrid nanogenerator (TPHG) is constructed with a synergy output of triboelectric and piezoelectric effects. The Zn-Car_TPHG demonstrates a high output performance (131 V at 100 kPa) and a wide range of pressure response (1 Pa–100 kPa), possessing applications in environmental energy collection and biomedical sensors. To expand the application of the wearable device, a conductive hexagonal prism MOF (Cu3(2,3,6,7,10,11-hexahydroxytriphenylene)2 (Cu-HHTP)) is synthesized and employed to load thymol (Thy). Cooperating with Zn-Car_TPHG, the resulting Cu-HHTP/Thy can achieve an efficient self-powered ROS (singlet oxygen (1O2) and hydroxyl radical (·OH)) generation and drug synergistic broad-spectrum sterilization effect (efficiency ≥ 98%). In a word, the flexible wearable device based on the muti-functional Bio-MOFs is sustainable and environmentally friendly, possessing wide application potential in fields of environmental energy collection, biosensors, and self-powered antibacterial.