Dental hypersensitivity (DS) is one of the most common diseases in the United States, affecting the majority of the adult population. DS is commonly accompanied by gingival recession and occurs at the cervical third of the crown. DS is usually triggered externally, e.g. by cold, hot, acid, or basic conditions in the saliva, and produces a sharp pain at the root of the tooth. Our objective is to develop a biomimetic treatment protocol comprising a peptide gel formulation to treat DS. Current approaches include desensitizing nerve ends by blocking the axonic action via potassium salts, limiting the permeability of dentinal tubules using synthetic adhesive sealers, e.g. NaF, bioactive glasses, oxalic acid and glass ionomer cements, or forming coagulates inside the tubules using protein cross-linker agents. Although these agents may be effective, clinical validation is still lacking and their short durability against daily tooth brushing, various foods, or drinking of acidic beverages makes their occlusion effects incomplete. We propose to form a mechanically and thermally stable mineral layer and thereby occlude exposed dentinal tubules using a peptide-remineralization approach. Working closely with the Dental School, our approach involves exposing underlying dentin by removing cement tissue at the coronal root surface by scraping away dentin on extracted human tooth to mimic hypersensitivity conditions. The samples are next treated with peptide-enabled remineralization resulting in tens of micrometer-thick new layer over the damaged dentin. The stability of the newly formed layer is then mechanically and thermally evaluated using nanomechanical testing and thermal-cycling, respectively. Our results demonstrate that exposed dentinal tubules are successfully occluded by mechanically and thermally stable mineral layer. Through a molecular biomimetic approach, the method described herein offers a unique solution to dentinal hypersensitivity, which can be used as a platform technology to develop effective in-clinic and over-the-counter hypersensitivity treatments.