Activation of G-protein-coupled receptors (GPCRs) initiates signal transduction cascades that affect many physiological responses. The worm Caenorhabditis elegans expresses> 1000 of these receptors along with their cognate heterotrimeric G proteins. Here, we report properties of 9-cis-retinal regenerated bovine opsin [(b) isoRho] and human melanopsin [(h) Mo], two light-activated, heterologously expressed GPCRs in the nervous system of C. elegans with various genetically engineered alterations. Profound transient photoactivation of G i/o signaling by (b) isoRho led to a sudden and transient loss of worm motility dependent on cyclic adenosine monophosphate, whereas transient photoactivation of G q signaling by (h) Mo enhanced worm locomotion dependent on phospholipase Cβ. These transgenic C. elegans models provide a unique way to study the consequences of G i/o and G q signaling in vivo with temporal and spatial precision and, by analogy, their relationship to human neuromotor function.—Cao, P., Sun, W., Kramp, K., Zheng, M., Salom, D., Jastrzebska, B., Jin, H., Palczewski, K., Feng, Z. Light-sensitive coupling of rhodopsin and melanopsin to G i/o and G q signal transduction in Caenorhabditis elegans.