This study aimed to evaluate the effectiveness of Teethmate desensitizer, a dentin bonding agent (DBA), Nd:YAG laser, and Er:YAG laser, which provides dentin tubule occlusion in the pulp chamber with different mechanisms, in preventing tooth discoloration due to regenerative endodontic treatment. One hundred five extracted maxillary human incisors with single roots and single canals were included in the study. The apical third of each tooth was resected below the enamel-cementum junction (CEJ) to obtain a standard root length as 10 ± 1mm. Root canal preparation was performed using the ProTaper Next files up to X5. Root canals were prepared with Gates Glidden (# 2-4) burs to simulate the immature root apex and an apical diameter of 1.1 ± 0.1mm was obtained. The teeth were randomly divided into 7 groups (n = 15): DBA, Teethmate, Nd:YAG, Er:YAG, Biodentine, Blood, and Negative Control. Relevant dentin tubule occlusion methods were applied to DBA, Teethmate, Nd:YAG, and Er:YAG groups. Following dentin tubule occlusion procedures, Biodentine was placed on the blood clot after filling the root canals with blood up to 4mm below the CEJ. No dentin tubule occlusion procedure was applied for Blood and Biodentine groups. Color measurement was performed with the spectrophotometer Vita Easyshade Advance before treatment, immediately after treatment, and at days 7, 30, and 90. Data were converted to L*a*b color values of Commission International de I'Eclairage (CIE L*a*b) and ΔE values were calculated. Two-way ANOVA and post hoc Tukey test (p = 0.05) were performed for statistical analysis. A clinically detectable color change was observed in all groups except for the negative control (ΔE ≥ 3,3). It was observed that Biodentine used alone has a potential for discoloration. It was determined that as the contact time with blood increased, tooth discoloration increased. However, no significant difference was found between dentin tubule occlusion methods in preventing color change (p > 0.05). It was determined that no dentin tubule occlusion method could 100% prevent discoloration caused by RET. DBA and Teethmate, which do not have a significant difference in terms of preventing color change, are considered to be suitable for dentin tubule occlusion due to their ease of application and low cost compared to Nd:YAG laser and Er:YAG laser.