Layer II neurons of the entorhinal cortex (ECII) are selectively vulnerable to Alzheimer’s disease (AD). Investigations into the molecular mechanisms of this ECII vulnerability provide unique opportunities to better understanding the pathology of AD. Preliminary data has suggested teneurin-3 (Tenm3) to have a role in this vulnerability due to its ECII enrichment, genetic variants associated with AD, and altered electrophysiology in Tenm3-knockout (KO) mice. In this study, the impacts of Tenm3- KO in mice were further explored. Electron tomography and immunofluorescent confocal microscopy were utilized to compare wild-type (WT) and KO mice’s perforant pathway synaptic densities and structures. A slight trend was found for increased synaptic density in Tenm3-KO mice. The structural changes in Tenm3-KO mice were more pronounced and encompassed alterations to active zones, bouton volumes, and synaptic vesicle pools. Overall, this work suggests Tenm3’s involvement in structural remodeling of both axonal boutons and dendritic spines thus providing a hypothesis for its role in ECII’s selective vulnerability to AD.