Aim: The aim of this split-mouth, blinded randomized controlled trial was to evaluate the clinical and radiographic effects of locally delivered 1,25 dihydroxycholecalciferol (1,25 DHC) on the amount of canine distalization. Materials and methods: Fifteen patients between age groups of 15 years to 30 years willing to undergo orthodontic treatment in a dental college participated in the study. A computer-generated randomization list was generated to divide the maxillary arch into experimental side and control side. Allocation concealment was applied. Canine distalization was initiated using nickel–titanium (NiTi) closed coil springs delivering a force of 150 g per side, which was attached to the maxillary first molar tube and canine hook. Local periodontal gel injection of 1,25 DHC was given on the experimental side and placebo gel on the control side at distal side of the maxillary canine at monthly interval, respectively. Patients were evaluated from beginning (T₀), 4 weeks (T₁), 8 weeks (T₂), and 12 weeks (T₃). CT scans were taken at T₀ and T₃ to measure the changes in bone density. The difference in amount of canine distalization and the changes in bone density were assessed on the experimental and control sides, respectively. Descriptive statistics and paired t test were used to determine any differences. Results: The results showed statistically significant increase in the amount of canine distalization and decrease in cancellous bone density on the experimental side when compared to control side. Conclusion: The active form of vitamin D can be an effective agent to accelerate orthodontic tooth movement (OTM). Clinical significance: This study provides a new insight into the scope of vitamin D in clinical orthodontics and its innovative method of application to accelerate tooth movement in patients will revolutionize treatment as well as open newer boundaries in orthodontic research at a biomolecular level.