Wrinkling, formed by stress-induced energy minimization in thin polymer films, provides a reproducible method for large-area surface patterning. The resulting nano/micro topographies allow controlled spatial organization of nanomaterials for applications in sensing, optoelectronics, photocatalysis, and soft nanofabrication. The anisotropy of these wrinkled patterns can also be tuned for anti-biofouling or directional templating of biomolecules, which is crucial for hybrid bio-interfaces. Complementing this, spider silk-based surface technologies offer a flexible platform for creating biocompatible and biodegradable coatings. Recombinant spider silk protein technologies enable the modification of intrinsic protein properties (e.g., net charge) or incorporation of new functional elements (e.g., affinity peptides, enzymes). Spider silk-based coatings have been engineered for antifouling activities or to support cell adhesion and growth. In terms of biomedical applications, enhanced implant performance is feasible as well as tailored tissue engineering approaches. The synergistic combination of wrinkling and recombinant spider silk technology presents exciting opportunities for creation of surfaces with enhanced or new functionalities. For instance, spider silk wrinkled coatings can provide benefit for bioelectronics by encapsulating sensitive biomolecules within a topographically defined matrix, increasing sensitivity and specificity. This approach also offers innovations in biomedical device coatings, tissue engineering platforms (e.g., for neuronal or muscle tissue), large-scale bio-selective filtration, and switchable sustainable adhesives.