Indirubin (INR), a red structural isomer of the blue indigo (IND) shows, for an organic dye, a high stability towards light. The nature of this photostability is unknown and is here proposed to be linked to efficient dark processes dominating the excited state deactivation. As with IND, an excited state proton transfer (ESPT) process, together with the possibility of rotation around the central carbon-carbon bond (with formation of a syn-rotamer) are, solvent dependent, active molecular mechanisms of the decay pathways in INR. To equate this behaviour, INR, together with N-methyl-(MINR) and N,N′-dimethyl-indirubin (DMINR) have been synthetized and fully investigated from a combination of steady-state, fast-transient absorption and fluorescence techniques together with TDDFT electronic calculations. To rationalize the behaviour of INR in water, the water-soluble sulfonated indirubin (5SINR) and the tri-sulfonated indigo (3SIND) were further investigated. For INR in viscous solvents (e.g. glycerol) ESPT is present. With the studied indirubin derivatives (exception made to DMINR), an additional pathway, to ESPT, exists involving rotation between the two indole-like moieties, with a syn-conformer, leading to a more efficient radiationless deactivation pathway, when compared to indigo. The mechanism of syn-conformer formation is found to involve a longer lifetime in the viscous solvent. This new deactivation process is not present in IND. ESPT, found to be enhanced in water via intermolecular water assisted proton transfer, with a kinetic isotopic effect (KIE = k_H/k_D), equal to 2 for 3SIND, is also found present for 5SINR with a KIE = 1.5. The common structural origin of the N–H⋯OC bonds in the DNA nucleotides and the indigoid dyes (INR and IND), introduces a new perspective for the study of the molecular protective mechanisms in these molecules.