Tissue adhesives are widely desired in surgical wound closure and interfacial modification of medical devices. However, poor adhesive strength, low mechanical compliance, high costs, and biotoxicity of traditional adhesives limit their biomedical applications. In this work, we fabricated a class of mussel-inspired polyurethane adhesives (MPUAs) with robust properties, including in situ gel formation under mild conditions, accommodation of intricate wounds, strong adhesion, and good biocompatibility. Dopamine-modified lysine (LDA), as a chain extender, was incorporated into linear polyurethane as a crucial adhesive unit, and biologically sourced lysine was used as a mild curing agent for in situ gel. The premixed polyurethane adhesives can be fluently injected and can fill irregular and complicated defects. After mixing for several minutes, the adhesives can strongly bond multiple substrates, such as metallic materials, organic materials, and inorganic nonmetallic materials. In particular, they can strongly cohere the fresh (wet) biological tissues with a ductile interface, and the lap shear strength (24.5 ± 2.0 kPa) of the MPUAs was six times higher than that of the commercial fibrin glue. Moreover, the bursting pressure of MPUAs on the porcine aorta was 108.2 ± 3.8 mmHg, which can satisfy most of the surgical requirements (≤20 mmHg). Given its good biocompatibility, this system would provide potential applications in clinical surgery and biological coatings of medical devices.