In this in vitro study, the effects of Stromal cell-derived factor-1 (SDF-1) was evaluated on the periodontal ligament-Mesenchymal Stem Cells (pdl-MSCs) functions. Real-time cell analyzer-single plate (RTCA-SP) was employed for proliferation, and RTCA-dual purpose (DP) was utilized for pdl-MSCs migration potential treated with different SDF-1 concentrations (0, 0.1, 1, 10, 100, 200, and 400ng/ml). Based on the dose-response findings, 10ng/ml SDF-1 was used for further mRNA experiments. RNAs isolated at 6 and 24h were checked using quantitative RT-PCR for mineralized tissue-associated genes including type I collagen (COL I), osteocalcin (OCN), osteopontin (OPN), and runt-related transcription factor 2 (Runx2). cRNA was synthesized for 6h, and whole-genome array analysis was performed for over 47.000 probes. Data were subjected to quantile normalization before analysis. Increased proliferation and migration were observed in pdl-MSCs treated with 0.1, 1, and 10ng/ml SDF-1. Increased COL I was observed at both time points: 6 and 24h. While there was no significant change for OCN, OPN, and Runx2 at 6h, SDF-1 up-regulated OCN and OPN, but down-regulated Runx2 mRNA expressions at 24h. IL-8 and ESM1 genes were differentially expressed over twofold when the pdl-MSCs were exposed to SDF-1 at whole-genome array analysis. IL-8 induction was confirmed with RT-PCR. Findings of this study displayed that SDF-1 modulated pdl-MSCs which were important for periodontal regeneration, inducing migration and proliferation, and regulating extracellular matrix synthesis in favor of the formation of new attachment.