Coumarin (COU) is an essential phenolic compound safeguarding plants under environmental constraints. Coumarin-induced salinity tolerance is reported in tomato, wheat and sorghum. However, the underlying mechanism by which COU mediates stress tolerance is not established, particularly under manganese (Mn) toxicity. Therefore, the present study was undertaken to examine COU-mediated regulation of Mn tolerance mechanism in sesame. Plants were subjected to two Mn levels (450 and 750 mg kg(-1)), given as MnSO4. Sesame seeds were primed in different doses of COU (0, 50, 100, and 150 mg L-1). Coumarin effects on photosynthesis, SPAD values, glyoxalase system, osmolyte accumulation, secondary metabolism, ROS generation and detoxification, ascorbate-glutathione cycle and ions homeostasis were studied in sesame. Our results manifested a notable drop in growth, chlorophyll contents, leaf relative water content, photosynthesis, and nutrient acquisition in plants under Mn toxicity. Further, excess Mn substantially increased oxidative damage mirrored as higher endogenous levels of hydrogen peroxide (H2O2), superoxide radical (O-2(center dot-)), malondialdehyde, and electrolyte leakage. Coumarin protected plants from oxidative injury by strengthening the activities of ascorbate-glutathione cycle enzymes under Mn toxicity. Histochemical studies revealed lesser H2O2 and O-2(center dot-) generation in plants administered COU under Mn toxicity. Besides, COU brought a significant fall in the methylglyoxal levels by increasing the activities of glyoxalase enzymes. Moreover, proline and glycine betaine accumulation were several folds greater in plants pre-treated with COU under Mn toxicity. Coumarin lessened chlorophyll degradation, bettered photosynthesis, and abridged oxidative injury that might have enhanced tolerance to Mn toxicity.