Here we report that, in neonatal mice, IGFBP2 neurons and astrocytes are distributed throughout the hippocampus and IGFBP2 is essential for neuronal development and information transmission of the hippocampus and cognitive behavior. Study from igfbp2-KO (igfbp2-/-) shows that IGFBP2 responsible for the proper development of learning and memory in neonatal mice, via expressions of both cytoskeletal protein SPAR and NMDAR subtype NR2B protein in the hippocampus. Electrophysiological study displays that IGFBP2 can directly trigger excitatory inputs onto CA1 pyramidal neurons with a non-optimal inhibitory input through Glutamatergic and GABAergic synapses, to facilitate hippocampal information transfer by enhancing intrinsic excitability and stimulation-induced spike transmission. Moreover, IGFBP2 functions represent a distinct feature in a cell-type specific manner, and influences both Hebbian and homeostatic plasticity and selectively acts with preferring evoked-activity-preferred “Hebbian Cell” at excitatory synapses. Morphological and igfbp2-KO studies demonstrate that IGFBP2 improves neurite-proliferation and elongation as igfbp2-/- leads to reduced numbers of pyramidal cells and interneurons, which impairs LTP and cognitive performance as well as reduced pyramidal neuron’s tonic excitation and this could be rescued by IGFBP2 treatment. By orchestrating excitatory and inhibitory inputs, IGFBP2 enhances E/I ratio, predominantly contributes to enhance LTP, mediated by NMDAR and IGFR1-initiated ERK1/2-MAPK signaling. Our results provide a novel insight into understanding of how IGFBP2 function as a crucial factor for cognition in the childhood and may be a novel neurotropic target for enhancing infant cognition during neuronal development.