Gemcitabine is a chemotherapeutic drug used to treat cancer; however, it has severe side effects. Therefore, we evaluated the anticancer potency of balanitoside, a folk medicine isolated from the edible fruits of Balanites aegyptiaca, using a mouse model of lung cancer induced by Urethane/butylated hydroxytoluene, either alone or in combination with gemcitabine. The results indicated that balanitoside, when administered alone or in combination with gemcitabine, exhibited antitumor activity against lung cancer by reducing tumor incidence, multiplicity, and average tumor size. It also decreased the proliferation of tumor cells, induced apoptosis, triggered cell cycle arrest at the G0/G1 phase, and caused a marked reduction in cancer stem cell markers, aldehyde dehydrogenase (ALDH-1) levels, and the CD133 (+ve) cell population. Balanitoside also modulated the levels of oxidative stress markers in lung tissues. The results indicate that balanitoside enhances the antitumor activity of gemcitabine and may represent a natural adjuvant medication for lung cancer.