Introduction: The major challenge in dental pulp engineering is to make a successful combination of stem cells and biomaterials with the aim of providing the differentiation of stem cells into odontogenic cell types. Among biomaterials, some types of pluronics have been reported to increase bone formation of stem cells. The effect of these pluronics on odontogenic differentiation has not been addressed yet. This study aimed to examine the effect of pluronics F68, F127, and P85 on odontogenic differentiation of stem cells derived from third molar tooth germs of young adults. Methods: Human tooth germ stem cells (hTGSCs) were induced to differentiate into odontogenic cells in the presence of different concentrations of pluronics. Differentiation efficiency was assessed by quantitative real-time polymerase chain reaction for determining expression messenger RNA levels and by immunocytostaining for determining the protein expression of odontogenic markers (ie, dentin sialoprotein, dentin matrix protein 1, bone morphogenic protein 2, bone morphogenic protein 7) by measuring alkaline phosphatase enzyme activity and lastly by von Kossa staining for determining mineralization. Results: The results revealed for the first time that F68 has a great potential to boost odontogenic differentiation of hTGSCs. P85 was found to reduce cell viability during differentiation. F127 was nontoxic to hTGSCs but did not have any effect on differentiation. Conclusions: The positive effect of F68 on odontogenic differentiation might enable more efficient pulp regeneration. Yet, the exact mechanism of how F68 alters the differentiation pattern of hTGSCs remains to be investigated in the future studies.