Despite advances in vaccine and antiviral drug development, preventing respiratory virus infection and transmission on a global scale remains a major challenge. A notable limitation of these approaches is that they cannot provide strong protection at the site of initial infection—the respiratory mucosa. Currently, strategies to enhance mucosal immunity against respiratory pathogens are still lacking. We designed mucus-attached bispecific nanobodies intended to simultaneously neutralize viruses by binding to viral surface proteins and capture viruses by anchoring them in mucus. Compared with conventional non-mucus nanobodies, these mucus-binding bispecific nanobodies show enhanced retention in the respiratory tract, provide increased protection against influenza virus infection in mice, and reduce SARS-CoV-2 transmission in hamsters. Together, our findings represent a promising strategy to enhance mucosal defenses against respiratory viruses by blocking viral entry and limiting dissemination.