Cancer is a condition in which cell proliferation becomes unregulated and leads to unchecked and non-terminating growth. It is considered one of the most important causes of death throughout the world. Among all sorts of cancers, lung cancer is the most common and foremost cause of mortality. Late diagnosis and lack of efficient therapeutic intervention are the chief players that cause limitations in the treatment of this type of cancer. Two main types of lung cancer are small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Various therapeutic approaches have been evaluated against lung cancer treatment such as radiotherapy, chemotherapy, surgery, and immunotherapy. Cancer cells manifest resistance against chemotherapeutic drugs and become unable to halt the metastasis of tumor cells. In this notion, natural compounds always act as an alternative approach with fewer side effects from history. Natural compounds such as phytochemicals have been shown as promising therapeutic agents due to their apoptotic, antioxidative, and anti-inflammatory activities. In this chapter, the role of these natural compounds is elaborated and well-defined with their therapeutic targets. Flavonoids, phenols, alkaloids, quinones, naphthaquinones, bibenzyl, and carotenoids have been extensively used that may target apoptotic signaling pathways, halt metastasis, prevent the formation of new blood vessels and invasion of a tumor to the surrounding area. Moreover, the synergistic effect of chemotherapeutic drugs and natural compounds also potentially inhibits the growth and progression of tumor cells. All these aspects have been discussed in the present segment. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021.