Cisplatin (DDP) is widely used to fight lung cancer, but there is a risk of immune damage. Astragalus polysaccharides (APS) is the main active component of Astragalus membranaceus Bunge. It has demonstrated anticancer properties across a range of cancer types as well as to be effective against cisplatin induced immune damage. However, its therapeutic mechanism has not been fully explored. This study aimed to explore the antitumor mechanisms of APS and elucidate the relationship between APS and volatile organic compounds (VOCs) in exhaled breath of Lewis lung cancer (LLC) mice. Gas chromatography-mass spectrometry (GC-MS) was utilized to analyze the exhaled VOCs in LLC mice. A specific group of VOCs was identified as potential biomarkers for monitoring tumor progression. Furthermore, the effects of combined treatment with APS and DDP on the concentration of exhaled VOCs in LLC mice was evaluated. Stoichiometric analysis revealed that the levels of 12 VOCs exhibited substantial recovery following APS treatment. And a high concentration of APS (400 mg/kg), when combined with DDP, exhibited enhanced antitumor efficacy. The metabolic pathways involved in the action of APS include 12 pathways. Our methodology elucidated both the effects and mechanisms of APS on lung cancer, as well as the pharmacological enhancement of cisplatin by APS. These findings facilitate real-time monitoring of lung cancer treatments and contribute to the future development of anticancer therapies.