We report pH/bacteria-responsive nanocomposite coatings with multiple mechanisms of antibacterial protection that include the permanent retention of antimicrobials, bacteria-triggered release of antibiotics and bacteria-induced film swelling. A novel small-molecule-hosting film was constructed using layer-by-layer deposition of montmorillonite (MMT) clay nanoplatelets and polyacrylic acid (PAA) components, both of which carry a negative charge at neutral pH. The films were highly swollen in water, and they exhibited major changes in swelling as a function of pH. Under physiologic conditions (pH 7.5, 0.2 M NaCl), hydrogel-like MMT/PAA films took up and sequestered similar to 45% of the dry film matrix mass of the antibiotic gentamicin, causing dramatic film deswelling. Gentamicin remained sequestrated within the films for months under physiologic conditions and therefore did not contribute to the development of antibiotic resistance. When challenged with bacteria (Staphylococcus aureus, Staphylococcus epidermidis or Escherichia coli), the coatings released PAA-bound gentamicin because of bacteria-induced acidification of the immediate environment, whereas gentamicin adsorbed to MMT nanoplatelets remained bound within the coating, affording sustained antibacterial protection. Moreover, an increase in film swelling after gentamicin release further hindered bacterial adhesion. These multiple bacteria-triggered responses, together with nontoxicity to tissue cells, make these coatings promising candidates for protecting biomaterial implants and devices against bacterial colonization.