Drought stress induced by climate change is a major limiting factor for crop growth. Selenium (Se) is recognized as an important exogenous regulator that can mitigate drought and other abiotic stresses, but the effects of Se application at different growth stages remain unclear. In this study, greenhouse-grown tomato plants were subjected to four Se treatments (T1: control; T2: Se at seedling stage; T3: Se at flowering stage; T4: Se at both stages) combined with three irrigation regimes (W1: 50–55%, W2: 65–70%, W3: 80–85% of field capacity). The impacts of Se timing on antioxidant enzymes, osmotic regulators, and growth parameters were evaluated. Drought stress induced oxidative damage, reduced photosynthesis, and inhibited biomass accumulation, while proline content increased with drought severity. Se application showed clear growth-stage specificity: under mild stress, Se at the flowering stage most effectively enhanced antioxidant activity, regulated proline metabolism, improved photosynthetic performance, and promoted growth. Dual-stage application did not provide additional benefits. These findings indicate that applying Se during the flowering and fruiting stage is optimal for alleviating drought-induced growth inhibition in tomato. The results contribute to understanding Se-mediated drought tolerance and may support the development of stage-specific Se fertilizer management strategies.