Cranberry (Vaccinium macrocarpon) is known to have a therapeutic potential on human health. Several phytochemicals found in cranberry namely flavonol glysodies, proanthocyanidins and phenolic acids are known to contribute to its anti-microbial, antioxidant, and anti-inflammatory properties. In vitro studies have shown that cranberry may be potential therapeutic agents for the prevention and management of periodontal disease. This review focused on the beneficial effect of cranberry on oral and periodontal health and three possible mechanisms of action of cranberry on inhibiting the periodontal tissue destruction. Three possible targets of cranberry PACs include (i) periodontopathogens, (ii) host inflammatory immune response, and (iii) osteoclast differentiation and activity. Given that cranberry and its phytochemical constituents have shown beneficial effects in vitro, clinical trials are warranted to better evaluate the potential of these constituents for controlling and prevention of periodontal tissue destruction.