Bioluminescent optogenetics (BL-OG) is a neuromodulation platform that combines the genetic precision of optogenetics with the noninvasive delivery of chemogenetics. BL-OG employs luminopsins (LMOs), fusion proteins that tether a light-emitting luciferase to a light-sensitive opsin, enabling modulation of neural activity through either external illumination or internally generated bioluminescence following systemic delivery of a luciferin such as coelenterazine. The bioluminescent light produced by LMOs robustly drives neural activity, confirming that photon emission is sufficient to activate the opsin and modulate targeted neuronal populations in vivo. The emitted light also serves as a built-in optical readout of neuromodulation in real time. BL-OG effects can be tuned by adjusting luciferin dose or delivery parameters, and coupling BL-OG with focused ultrasound (FUS) enables spatially selective blood-brain barrier (BBB) opening for region-specific activation. Extending to larger-brained species such as marmosets, BL-OG offers a powerful, noninvasive tool for causal circuit dissection and translational neuromodulation.