Provided herein are compounds, compositions, and methods for modifying mucus, including modifying mucus using nitric oxide-releasing biopolymers (e.g., NO-releasing chitosan oligosaccharides). In some embodiments, a compound, composition, and/or method of the present invention modifies one or more properties of mucus to increase mucus clearance in a subject and/or prevents the growth or kills one or more pathogens present in mucus of a subject.