Introduction: The aim of this study was to present a systematic review investigating the gene expression of various cells (other than dental pulp cells) in response to different variants of tricalcium silicate cements (TSCs). Material and Methods: A systematic search of the literature was performed by two independent reviewers followed by article selection and data extraction. Studies analyzing any cell type except dental pulp stem cells and any variant of tri-calcium silicate cement either as the experimental or as the control group were included. Results: A total of 41 relevant articles were included in this review. Among the included studies, ProRoot MTA was the most commonly studied (69.1%) TSC variant, and 11 cell types were identified, with a majority of 13 articles investigating gene expression in osteoblasts. A total of 39 different genes/molecules expressed were found in the selected studies. The experimental group (irrespective of the TSC variant) was identified to express significantly increased gene expression than the control group (untreated) in all included studies. Discussion: Recent studies have provided useful insight into the gene expression and molecular signaling of various cells in response to TSCs, and new elements have been supplied on the pathways activated in this process. Conclusion: TSCs are capable of eliciting a favorable cellular response in periapical regeneration.