The present invention relates to topical oral care compositions comprising in a pharmaceutically acceptable carrier a safe and effective amount of a host-response modulating agent including one or more of an anti-oxidant and modifier of cell redox status, anti-inflammatory agent, metalloproteinase inhibitor, vitamins and nutrients key to maintenance of a host response balance and inhibitor of activation of NF-kB in combination with one or a mixture of additional oral therapeutic actives selected from antimicrobial/antiplaque agents, biofilm inhibiting agents, antibiotics; analgesics and local anesthetic agents; dentinal desensitizing agents and odor masking agents. The present compositions are effective in treating and preventing bacteria-mediated diseases present in the oral cavity and in mediating host reaction to the presence of pathogenic bacteria in the oral cavity as well as the toxins and endotoxins, inflammatory cytokines and mediators released or prompted by these oral pathogens. By controlling bacteria-mediated diseases and conditions present in the oral cavity and modulating host reaction, spread into the bloodstream and other parts of the body of pathogenic bacteria and associated harmful substances is prevented or minimized.