The present invention relates generally to nitric oxide-releasing suppositories and methods for their use. According to some embodiments of the present invention, a nitric oxide (NO)-releasing suppository (e.g., vaginal suppositories) is described. Some embodiments relate to compositions, kits, and / or methods for treating and / or preventing an infection (e.g., a viral infection). In some embodiments, a method is provided for treating and / or preventing a viral infection in a subject in need.