Bioadhesives have emerged as versatile and powerful tools for tissue repair and integration with biomedical devices, offering a wide range of applications that have captured significant clinical and scientific interest. Synthetic polypeptide adhesives are particularly promising candidates for bioadhesives, but often face limitations in adhesive strength. In this study, inspired by marine adhesive proteins, the secondary structure and hydrophobic–hydrophilic balance of polypeptides were precisely regulated to transform the polyelectrolyte to a strong adhesive. The resulting polypeptide adhesive demonstrated an adhesive strength exceeding 1.0 MPa, more than 10× higher than that of the previously reported synthetic polypeptide adhesive. The cohesion and adhesion of polypeptide adhesive can be optimized by adjusting the content of the secondary structure and hydrophobic residue ratios. More helices in polypeptides enhance the interactions between the polypeptide backbone and side chains as well as the interactions between polypeptides and substrates. In addition, these polypeptide adhesives exhibit excellent tolerance to strong acids or alkalis, remarkable adhesion to variable materials and tissues, and an impressive sealing performance.