Objectives Oxidative stress within the idiopathic pulmonary fibrosis microenvironment decreases the survival of lung mesenchymal stem cells (LMSCs), resulting in disease progression. Herein, the effects of curcumin (CUR) against hydrogen peroxide (H2O2)-mediated damage to murine LMSCs were examined. Methods Apoptosis, reactive oxygen species, and mitochondrial membrane potential were detected by flow cytometry. Protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated x (Bax), cleaved caspase-3, protein kinase B (PKB/Akt), phosphorylated-Akt, nuclear factor erythroid-2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were evaluated by western blot analysis. Results Apoptosis rates in the 2.5, 5, and 10 mu M CUR groups were 23.27% +/- 0.31%, 14.87% +/- 0.41%, and 6.47% +/- 0.50%, respectively, all of which were lower than in the H2O2 group (24.46% +/- 1.35%). Reactive oxygen species levels were decreased, while mitochondrial membrane potential levels were increased in concentration-dependent manners in the CUR groups compared with the H2O2 group. Compared with the H2O2 group, all CUR groups showed reduced cleaved caspase-3 expression, increased Nrf2 and HO-1 expression, and increased Bcl-2/Bax and p-Akt/Akt ratios. Conclusions The protective effects of CUR against H2O2-mediated damage in murine LMSCs may be mediated through the Akt/Nrf2/HO-1 signaling pathway.