Thiamethoxam (TMX), a second-generation neonicotinoid, is extensively used to control numerous pests that infest crops. We investigated the effects of TMX (10, 20, 30, 40, and 50 μg/mL for 24, 48, 72, and 96 h) on biomarkers such as antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)); malondialdehyde (MDA), protein, lipid, and carbohydrate levels; micronucleus formation; and total hemocyte count in a model organism, Galleria mellonella L. SOD and CAT activities significantly decreased after 72 and 96 h of treatment at all TMX concentrations compared with control. MDA level increased following treatment with all TMX doses, with the exception of that following treatment with the lowest dose (10 μg/mL) at all tested treatment durations. Lipid and carbohydrate levels significantly decreased following treatment with high doses of TMX (40 and 50 μg/mL) after 48, 72, and 96 h. Micronucleated cell number significantly increased following treatment with all TMX doses at all tested treatment durations, except with 10 μg/mL of TMX for 24 h, when compared with control. During the first 72 h, total hemocyte count significantly decreased following treatment with 20-, 30-, 40-, and 50-μg/mL TMX; however, it was significantly reduced at all doses of TMX after 96 h. These results suggest that TMX can induce immunotoxicity, oxidative stress, and genotoxicity in a potential target and also in the model organism, G. mellonella. In addition, our study provides additional information regarding the prospective toxic effects of TMX.