Melatonin is a well-known bioactive molecule able to mitigate photooxidative damage caused by excess light. Here we have shown that mutant Arabidopsis lines with disrupted genes for melatonin putative receptor CAND2/PMTR1 and GPA1 encoding the α-subunit of heterotrimeric G-protein were partially insensitive to melatonin treatment under high light stress. They exhibited a higher degree of photodamage due to a significantly decreased photosynthetic activity and diminished expression of chloroplast and nuclear-encoded genes and the corresponding proteins. A possible mechanism for melatonin-dependent regulation of chloroplast genes is associated with a change in the activity of the genes for chloroplast RNA polymerases. We conclude that under high light stress, melatonin may act as a hormone-like signaling molecule via the CAND2/PMTR1-mediated signaling pathway.