Objectives To address the lack of nerve and blood supply after labial salivary gland transplantation (LSGT) resulting in glandular atrophy. We designed a modified LSGT, called insular infraorbital neurovascular pedicle LSGT, and evaluated the postoperative efficacy. Design This is a prospective, single-centre, self-contained study. Setting The research was conducted at Beijing Tongren Hospital, Capital Medical University from July 2019 to March 2024. Participants Eight patients (nine eyes) with severe dry eye disease (DED) were enrolled in this study. Interventions All patients underwent insular infraorbital neurovascular pedicle LSGT and were followed up for at least 6 months postoperatively. Main outcome measure Key evaluation indices were best-corrected visual acuity (BCVA), Ocular Surface Disease Index (OSDI) score, tear break-up time (TBUT), Corneal Fluorescence Staining (CFS) score, and Schirmer I test (SIT). Results With a mean follow-up of 17.56 +/- 11.72 months, BCVA improved in four eyes and stabilized in five. OSDI score decreased from 59.33 +/- 14.37 to 26.27 +/- 10.14 (p<0.001). SIT improved from 0.00 +/- 0.00 mm to 5.44 +/- 2.01 mm (p<0.0001). TBUT increased from 0.23 +/- 0.48 s to 5.48 +/- 4.67 s (p=0.008). CFS scores decreased from 12.56 +/- 2.65 to 7.56 +/- 3.09 (p<0.001). All glands remained viable with good blood supply, and no serious complications were observed. Conclusion Insular infraorbital neurovascular pedicle LSGT for severe DED is a feasible and effective treatment, maintaining good secretory capacity and blood supply long-term.