The development of nanoagrochemicals has attracted much attention in the last decade to overcome the recent agricultural and environmental challenges associated with the intensive usage of insecticides. Herein, nanostructured calcium borate materials with hierarchical sea urchin-like microspheres and microblocks have been synthesized by a facile hydrothermal method. The insecticidal activity of CaB2O4 and its synergistic combination with cholinesterase-inhibiting insecticides are explored against Spodoptera littoralis (S. littoralis) for the first time via a feeding bioassay protocol. The insecticidal efficacy of sea urchin-like microspheres (CB-A) is estimated to be LC50 = 207 mg L-1 which is two-fold higher than that of microblocks (CBM-A) with LC50 = 406 mg L-1 after eleven days of exposure. The synergistic combination of the CB-A sample with methomyl and chlorpyrifos increases the toxicity to 2.4 and 2.6-fold higher than that of the individual insecticides, respectively. Significantly, sea urchin-like CaB2O4 microspheres cause physical damage to the external insect's cuticle layer, which consequently enhances the uptake of organic insecticides. Our results revealed that calcium borate micro-/nano-structures can be employed as a multifunctional nanoagrochemical in various agricultural programs for S. littoralis control and decrease the usage of cholinesterase-inhibiting insecticides.