Background: Interstitial lung diseases (ILD) are chronic inflammation and fibrosis of lung tissue, affecting interstitial, alveolar, and vascular areas of the lungs. Aim: To assess the effect of vitamin D (VD) supplementation in treating ILD cases, excluding connective tissue-associated interstitial lung diseases Patients and methods: This investigation was a randomized controlled trial involving 104 cases with interstitial lung disease who looked for evaluation and therapy at the Chest Department in collaboration with the Chemical Pathology Department at Kasr Al-Ainy Hospital, Cairo University. The investigation has been performed from February 2019 to November 2019. Results: Following three months of VD supplement, the serum VD level significantly rose from 5.7 to 18.5 (nanogram per milliliter), with a with a P-value less than 0.001. Regarding the score of dyspnea, it significantly decreased from 3 to 2, P < 0.001. The spirometery readings of the cases showed improvement at the level of large airways, as both FEV1% and FVC were significantly enhanced (P = 0.02 and 0.004), correspondingly, while at the small airways level, the improvement failed (P = 0.3). Considering the patient's ability to do a 6-minute walk test (6MWT), it significantly improved and subsequently the patient's oxygenation (P = < 0.001, 0.01 and 0.03), respectively.