Previous work from our group demonstrated that pregnant mice exposed to marijuana smoke presented reduced fetal and neonatal outcomes including reduced birthweight and increased placental weight. To further characterize the possible placental mechanisms underlying these observations, the present study evaluated placental morphology, function and molecular markers in the same experimental model. Female mice were exposed to Cannabis sativa smoke or filtered air daily from gestational day (GD) 0.5 to 18.5 GD. At 18.5 GD, pregnant females were euthanized and placentas were analyzed. Results showed that exposure to Cannabis sativa smoke reduced fetal weight and increased placental weight compared to control animals. Stereological analyses revealed increased volumes of labyrinth and decidua compartments, increased capillary surface area, and decreased thickness of the interhemal membrane. Immunohistochemistry demonstrated increased expression of CB2 receptor and glucose transporter GLUT1. There were no differences between groups in HIF-1a and VEGF expression or in umbilical artery Doppler parameters. These findings suggest that gestational exposure to marijuana smoke alters placental morphology in a manner consistent with compensatory adaptation, possibly in response to reduced oxygen availability.