Introduction: Two important growth factors namely transforming growth factor- β (TGF-β) and Insulin-like growth factor (IGF-1) are known to provide protection to dental pulp cells when cultured against the toxicity induced by the composite materials e.g. Durafill VS and Flow Line. Aim: Protective mechanism of IGF-1 and TGF-β is mainly via enhanced endogenous antioxidant activity because the toxicity of composite materials is mainly governed by oxidative stress. The present study was planned to investigate the protective effect of growth factors. Methods: Cultured dental pulp cells were used in current study to determine the mechanism of the protective effects of IGF-1 and TGF-β and their role of cysteine/glutamate exchange (system xc) focusing on the glutathione system. Results: The toxicity of Durafill VS and Flow Line was debilitated by the addition of glutathione monoethylester, suggestive of a specific role of anti-oxidant glutathione. In support of this hypothesis, it was found that IGF-1 and TGF-β had protective effect against the toxic effect of buthionine sulfoximine (glutathione synthesis inhibitor). Cellular cysteine levels are considered to be the limiting factor in glutathione production therefore, effects of IGF-1 and TGF-β were tested on cysteine uptake which were found to stimulate system xc–guided cysteine uptake. Furthermore, they dissipated the glutathione depletion induced by Durafill VS and Flow Line. Conclusions: The results were suggestive of protective role of IGF-1 and TGF- β through system xc– guided cysteine uptake stimulation, leading to maintenance of cellular glutathione. This novel role of growth factors IGF-1 and TGF-β helps in pre-venting toxicity of restorative dental materials and also in the general functioning of dental pulp cells.