OBJECTIVE: This clinical study evaluated an experimental pregabalin (PG) gel in reducing dental sensitivity (DS) and color change after dental bleaching. MATERIALS AND METHODS: Seventy-five volunteers were selected and randomized into three groups: GPG (10% pregabalin gel), GKF (5% potassium nitrate and 2% sodium fluoride), and GP (placebo gel). Prior to the bleaching treatment, GPG and GKF received applications of the respective desensitizing gels for 10 min. The GP group received an application of placebo gel, similar to the other groups. The bleaching was performed with 35% hydrogen peroxide in 3 sessions, with a 7-day interval between sessions. Post-bleaching DS was assessed using the visual analog scale (VAS) over 21 days of follow-up. Color Assessment (ΔE00, ΔWID, and ΔEab) and luminosity (L) were measured at baseline (T0) and 7 days after the third session (T1). Friedman, Kruskal-Wallis, one-way ANOVA, and Tukey tests were used, with α = 5%. RESULTS: Intergroup analysis showed that on the 1st, 8th, and 15th days, DS was higher for GP (p <
0.006
p = 0.004
p <
0.002) and did not differ between GKF and GPG (p = 0.203
p = 0.178
p = 0.09). In the intragroup analysis, GP showed a significant increase in DS on the 15th day (p <
0.002). CONCLUSIONS: The experimental 10% pregabalin gel reduced dental sensitivity and did not interfere with bleaching results. CLINICAL SIGNIFICANCE: The topical application of 10% pregabalin gels and NKF was effective in reducing tooth sensitivity 24 hoursafter whitening with 35% hydrogen peroxide. TRIAL REGISTRATION: ClinicalTrials.gov trial registry with the identifier NCT06180707.