Described herein are antimicrobial nanoclay comprising two or more cationic antimicrobials. The nanoclay is a phyllosilicate clay and the two or more cationic antimicrobials are individually selected from the group consisting of a quaternary ammonium compound, a metal ion-containing, a cationic chelating agent, a cationic amino acid-based surfactant, a cationic antibiotic, and a cationic compound having a guanidine moiety. The two or more different antimicrobials are incorporated into the nanoclay by a cationic exchange process. Also described are methods for preparing such antimicrobial nanoclays. The antimicrobial nanoclays may be used for conferring antimicrobial activity to an article of manufacture and/or for providing antimicrobial activity to a surface.