Modern progress in photopharmocology calls for new generation of compounds joining bioactivity, photoswitchable properties and high selectivity of response to light wavelength. Introduced here, phosphonate–fullerene hybrids are the first representatives of such compounds. Phosphonate–fullerene hybrids were synthesized on a base of fullerene C₆₀ and organophosphates with the function of photoswitchable cholinesterase activity—phosphorylated thiazolotriazole and aminomalonate compounds and studied with FTIR, UV–VIS spectroscopy and IPC-micro neurotoxin amperometric analysis. As a result of spectroscopic and bioactivity characterization, it was not only demonstrated butyrylcholinesterase (BuChE) inhibition increase in phosphonate–fullerene hybrids compared with pure phosphonates but also pronounced response of inhibition degree to laser irradiation of hybrids. It was found opposite behavior of hybrids as a result of laser irradiation—BuChE inhibition drop-off for thiazolotriazole–fullerene and pronounced growth for aminomalonate–fullerene. The other remarkable peculiarity of presented phosphonate–fullerene hybrids is high selectivity of inhibition change degree to laser wavelength (266 or 325 nm).