One potential solution to the rising threat of antibacterial drug resistance is the application of therapeutic clays to treat wound infections. Clays with antibacterial activity have been identified from a range of sources with their antibacterial properties often attributed to the release of toxic metal ions such as Fe(II) and Al(III). Here, clays from Afghanistan, Azerbaijan and Bangladesh that are utilized for washing and healing purposes were examined. Their antibacterial activities were assessed in suspension and as aqueous leachates against representative Gram-negative, Escherichia coli, and Gram-positive, Bacillus subtilis, bacteria. The majority of the clays conferred no deleterious effect and, in fact, tended to promote bacterial growth, likely as a result of released organic and inorganic nutrients. However, one of the clays, obtained from the Dhaka region of Bangladesh, displayed significant bactericidal activity against E. coli and B. subtilis as a clay suspension but not as an aqueous leachate. Further experiments confirmed that contact between clay and the bacteria was necessary for most of the antibacterial effects. Detailed analysis of bulk and <2 μm clay fraction mineralogy and geochemistry revealed no single defining parameter or mineral component that could be used to easily distinguish natural clays with antibacterial properties from those without. Overall, the results suggest a mechanism of antibacterial action of the Dhaka clay that arises from acidic conditions, likely enabled by the absence of calcite in the bulk clay, metal release, the presence of interstratified chlorite-smectite, and direct clay–bacteria interactions.