B vitamins rescue cleft palate induced by glucocorticoids in rodents; however, the mechanism of this effect remains largely unknown. The objective of our study was to assess the effect of dexamethasone and Vitamin B12 on cell proliferation and apoptosis during palatogenesis. In our study, mesenchymal cell proliferation in mouse embryonic palates decreased when the subjects were administered dexamethasone at embryo day 13.5 (E 13.5). However, mesenchymal cell proliferation was increased after dexamethasone exposure at E 14.0 and E 14.5 in comparison with the control group. After Vitamin B12 treatment, proliferation of mesenchymal cells was restored. No apoptosis was detected until bilaterial palatal shelves adhered and formed a medial epithelium seam in the control group and Vitamin B12-treated group. However, the apoptotic cells were detected under the medial edge epithelium before the palate contacted after dexamethasone treatment. The results suggested that Vitamin B12 restored proliferation, which had been reduced by dexamethasone via a delayed cellular cycle and apoptosis. This study implies that Vitamin B12 may be used to prevent or alleviate cleft palate induced by dexamethasone during embryonic palatogenesis.