Acute lung injury (ALI) is a life-threatening disorder featured by pulmonary inflammation, with no highly effective pharmacological treatments available. Given the anti-inflammatory property of garlic (Allium sativum L.) and the therapeutic potential of plant-derived nanovesicles, we hypothesized garlic-derived exosome-like nanovesicles (GAELNs) protect against ALI. In our present study, GAELNs were successfully isolated, purified, and characterized, showing typical exosomal traits and diverse biomolecules. In vivo, GAELNs administration mitigated LPS-induced lung histopathological damage and suppressed pro-inflammatory cytokine production. In vitro, GAELNs were efficiently internalized by RAW264.7 macrophages, leading to reduced secretion of harmful cytokines. Transcriptomic profiling indicated that the anti-ALI effects of GAELNs were associated with modulation of multiple inflammatory signaling pathways. Mechanistically, GAELNs conferred protection by potently inhibiting the cGAS-STING signaling axis and its downstream effectors. Collectively, GAELNs alleviate ALI by inhibiting the cGAS-STING mediated inflammatory cascade, representing a promising novel therapeutic strategy for ALI.