The recently prepared nanophotocatalyst Ni-NiO is introduced as an effective mediator in the one-pot two-component synthesis of various substituted bis(indolyl)arylmethanes and as potent anti-lung cancer agent. The inception of this environmental friendly photocatalyst stems from the biosynthesis process utilizing Glycyrrhiza Glabra (licorice) leaves extract that is an active plant with potential applications in lung cancer treatment. Familiar characterization techniques including XPS, UV–Vis, XRD, FT-IR, FE-SEM, TEM, and EDS provided a comprehensive information on the physicochemical properties of Ni-NiO nanoparticles. Subsequently, the Ni-NiO nanophotocatalyst was harnessed for the synthesis of bis(indolyl)arylmethanes under visible light. The utilized photocatalyst underscored reasonable stability, reusability, and practical utility. Moreover, cytotoxicity evaluations employing the MTT experiment on A549 lung cancer cell line proved promising potential of Ni-NiO nanoparticles and bis(indolyl)phenylmethane in inhibiting cancer cell proliferation. Findings revealed that both biosynthesized Ni-NiO nanoparticles and the tested bis(indolyl)phenylmethane have sufficient therapeutic potential against the performed cancer cell line. This innovative approach represents a significant contribution to the field of cancer research and underscores the potential for developing next-generation cancer treatments.