Singlet molecular oxygen (¹O₂) is one of the major agents responsible for (photo)oxidative damage in biological systems including human skin and eyes. It has been reported that the neural hormone melatonin (MLT) can abrogate ¹O₂-mediated cytotoxicity through its purported high antioxidant activity. We studied the interaction of MLT with ¹O₂ in deuterium oxide (D₂O), acetonitrile and methanol by measuring the phosphorescence lifetime of ¹O₂ in the presence of MLT and related indoles for comparison. Rose bengal (RB) was used as the main ¹O₂ photosensitizer. The rate constant (k_q) for the total (physical and chemical) quenching of ¹O₂ by MLT was determined to be 4.0 × 10⁷ M^–1 s^–1 in D₂O (pD 7), 6.0 × 10⁷ M^–1 s^–1 in acetonitrile, and 6.1 × 10⁷ M^–1 s^–1 in methanol-d₁. The related indoles, tryptophan, 5-hydroxyindole, 5-methoxytryptamine, 5-hydroxytryptamine (5-OH-T, serotonin), 6-hydroxymelatonin (6-OH-MLT) and 6-chloromelatonin quenched ¹O₂ phosphorescence with similar k_q values. We also compared the photosensitized photobleaching rate of MLT with that of other indoles, which revealed that MLT is the most sensitive to ¹O₂ bleaching. Hydroxylation of the indole moiety in 5-OH-T and 6-OH-MLT makes them more sensitive to photodegradation. In the absence of exogenous photosensitizers MLT itself can generate ¹O₂ with low quantum yield (0.1 in CH₃CN) upon UV excitation. Thus, the processes we investigated may occur in the skin and eyes during physiological circadian rhythm (photo)signaling involving MLT and other indoles. Our results indicate that all the indoles studied, including MLT, are quite efficient yet very similar ¹O₂ quenchers. This directly shows that the exceptional antioxidant ability proposed for MLT is unsubstantiated when merely chemical mechanism(s) are considered in vivo, and it must predominantly involve humoral regulation that mobilizes other antioxidant defenses in living organisms.