Background and Aim: This study evaluated and compared the immediate and 2-month desensitizing efficacy of Gluma Desensitizer, Seal and Protect sealant, fluoride varnish, and erbium, chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser in reducing cervical dentin hypersensitivity (DH). Materials and Methods: Sixty patients each with at least one hypersensitive premolar were selected and randomly assigned to four groups: Gluma Desensitizer, Seal and Protect sealant, Duraphat fluoride varnish, and Er,Cr:YSGG laser. The assessment method used to quantify sensitivity was the cold air syringe, and the sensitivity was recorded by the visual analog scale (VAS), before treatment (baseline), immediately after treatment, and after 1, 2, 3, and 8 weeks. Results: The study results showed that there was a significant reduction in sensitivity at the various time intervals with all the four desensitizing agents – glutaraldehyde in methacrylate resin (Gluma Desensitizer), nanofilled methacrylate resin (Seal and Protect), sodium fluoride varnish (Duraphat), and Er,Cr:YSGG laser therapy. Conclusion: It can be concluded that after 8 weeks of clinical evaluation, all therapies showed lower VAS sensitivity values compared with baseline, independently of their different modes of action. The study indicates that Er,Cr:YSGG laser can emerge as an efficient treatment alternative in the reduction of DH.