The clinical efficacy of non-small-cell lung cancer (NSCLC) treatment is significantly hindered by Taxol resistance, demanding the exploration of novel approaches to overcome this challenge. Natural products, renowned for their diverse anticancer potential, offer hope, with allicin emerging as a captivating contender. However, the intricate role and underlying mechanisms of allicin in NSCLC Taxol resistance remain largely unexplored. In this extensive investigation, we delve into the impact of allicin on Taxol resistance, meticulously examining both in vitro and in vivo scenarios. Remarkably, allicin effectively curbs the proliferation and migration of A549/Taxol cells while inducing apoptosis. Unraveling the regulatory potential of genes like CDK1 in the cell cycle pathway, allicin demonstrated the ability to arrest cells in the G2/M phase, thus disrupting the cell cycle and heightening Taxol sensitivity. Strikingly, when combined with Taxol, allicin showed the ability to promote Taxol to inhibit tumor growth and reduce lung nodules in tumor-bearing mice, all without significant toxicity. Importantly, allicins prowess in reversing Taxol resistance via cell cycle regulation sheds light on its potential as a resistance-reversing agent in NSCLC, marking a vital milestone in the quest for natural source therapies.