Helicobacter pylori infection is associated with chronic gastritis, peptic ulcers, and gastric cancer. The effects of Solanum lyratum extract (SLE) on anti-H. pylori activity and H. pylori-induced apoptosis were investigated. SLE showed a moderate ability in inhibiting growth of H. pylori and also in interrupting the association of bacteria with host cells. SLE was also able to suppress H. pylori-induced apoptosis. SLE inhibited caspase-8 activation, thereby preventing the release of cytochrome c from mitochondria and activation of the subsequent downstream apoptotic pathway. Thus, SLE may offer a new approach for the treatment of H. pylori by down-regulation of apoptosis in the H. pylori infected gastric epithelium. As it does not directly target bacteria, SLE treatment might not cause development of resistant strains.