Widely used in humans and animals for bacterial infection management, antibiotics are poorly absorbed and persistent, being excreted into ecosystems and causing serious pollution. However, the effects of extended exposure to residual environmental levels of antibiotics in fireflies are currently unknown. In this study, we investigated Aquatica leii growth and development under chronic low-dose exposure to oxytetracycline (OTC) and levofloxacin (LEV) residues using physiology, transcriptomics, and metabolomics. The results showed that OTC and LEV treatments enhanced A. leii larval growth (increased body length and weight) and significantly altered SOD and CAT activities. Transcriptional analyses identified 1193 and 1669 differentially expressed genes from the LEV and OTC groups, respectively, compared to the control group, predominantly associated with insect hormone biosynthesis, digestive system, immune system, and signal transduction. The metabolomic results showed that 965 and 1094 endogenous metabolites (i.e., comprising mainly amino acids, organic acids, and carbohydrates) were affected by LEV and OTC treatments, respectively. These metabolites are mainly enriched in signal transduction, amino acid metabolism, and energy metabolism pathways. Further, a conjoint omics analysis highlighted the multifaceted regulatory roles of glutathione metabolism in the response of A. leii to OTC and LEV treatments. The study provides critical insights into the transcriptional and metabolic responses of A. leii to antibiotic treatment, informing dosage guidelines for sustainable A. leii farming.