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Background Gut microbiota may influence the efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC), but the clinical impact of microbiota-modulating interventions remains unclear. We conducted a meta-analysis to assess the associations of antibiotics and probiotics with immunotherapy outcomes in NSCLC and to examine their potential clinical relevance.Methods PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched up to November 30, 2025. Eligible studies included patients with NSCLC receiving ICIs and reported antibiotic or probiotic exposure with data on ORR, OS, or PFS; other microbiota-related strategies were reviewed descriptively when relevant. Studies without extractable outcomes and non-original reports were excluded.Results A total of 32 cohorts were included, comprising 27 antibiotic cohorts and 5 probiotic cohorts. Antibiotic exposure was not significantly associated with ORR, but was significantly associated with worse long-term outcomes, including shorter OS (pooled HR = 1.51, 95% CI 1.23-1.86, p < 0.001) and PFS (pooled HR = 1.53, 95% CI 1.36-1.73, p < 0.001). In contrast, probiotic supplementation was associated with improved efficacy across both response and survival endpoints, including higher ORR (pooled OR = 2.57, 95% CI 1.26-5.21, p = 0.01), longer OS (pooled HR = 0.37, 95% CI 0.26-0.54, p < 0.001), and longer PFS (pooled HR = 0.49, 95% CI 0.42-0.58, p < 0.001). These findings suggest opposite associations of antibiotic and probiotic interventions with immunotherapy outcomes in NSCLC, with no obvious evidence of publication bias.Conclusions Antibiotics and probiotics appear to exert opposite associations with immunotherapy outcomes in NSCLC. These findings support the microbiota as a clinically relevant host factor and provide a rationale for incorporating microbiota-related considerations into future guideline refinement, prospective clinical trials, and personalized immunotherapy strategies.