Objectives: This study aimed to investigate the effectiveness of different topical/systemic agents in reducing the damage caused by bleaching gel to pulp tissue or cells. Materials and Methods: Electronic searches were performed in July 2023. In vivo and in vitro studies evaluating the effects of different topical or systemic agents on pulp inflammation or cytotoxicity after exposure to bleaching agents were included. The risk of bias was assessed. Results: Out of 1,112 articles, 27 were included. Nine animal studies evaluated remineralizing/anti-inflammatories agents in rat molars subjected to bleaching with 35%– 38% hydrogen peroxide (HP). Five of these studies demonstrated a significant reduction in inflammation caused by HP when combined with bioglass or MI Paste Plus (GC America), or following KF-desensitizing or Otosporin treatment (n = 3). However, orally administered drugs did not reduce pulp inflammation (n = 4). Cytotoxicity (n = 17) was primarily assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on human dental pulp cells and mouse dental papilla Cell-23 cells. Certain substances, including sodium ascorbate, butein, manganese chloride, and peroxidase, were found to reduce cytotoxicity, particularly when applied prior to bleaching. The risk of bias was high in animal studies and low in laboratory studies. Conclusions Few in vivo studies have evaluated agents to reduce the damage caused by bleaching gel to pulp tissue. Within the limitations of these studies, it was found that topical agents were effective in reducing pulp inflammation in animals and cytotoxicity. Further analyses with human pulp are required to substantiate these findings.