Vitamin D deficiency in cigarette smokers (CS) might associate with several complications, including metabolic deficits, depression and anxiety. This study evaluated the effects of vitamin D on mental health symptoms, nicotine misuse, and biomarkers of metabolic diseases in individuals with a tobacco use disorder. A randomized, double-blind, placebo-controlled trial was conducted with 60 CS subjects receiving either 50,000 IU vitamin D supplements (n = 30) or placebo (n = 30) every 2 weeks for 24-weeks. Nicotine misuse, mental health scale, and metabolic parameters were measured before and after the intervention in the CS subjects. Compared with the placebo-group, after the 24-weeks intervention, serum 25 (OH) vitamin D levels increased in the intervention group (β 2.96; 95% CI, 0.91, 5.01; P = 0.006). In addition, vitamin D supplementation significantly improved Beck Depression Inventory (BDI) (β -2.06; 95% CI, -3.84, -0.28; P = 0.02). In addition, vitamin D administration significantly decreased fasting plasma glucose (FPG) (β -4.56; 95% CI, -8.94, -0.19; P = 0.04), insulin (β -0.50; 95% CI, -0.88, -0.13; P = 0.009), and homeostasis model of assessment-estimated insulin resistance (HOMA-IR) levels (β -0.21; 95% CI, -0.33, -0.08; P = 0.001). Furthermore, vitamin D resulted in a significant elevation in total antioxidant capacity (TAC) (β 81.20; 95% CI, 18.30, 144.11; P = 0.01), and plasma glutathione (GSH) levels (β 73.05; 95% CI, 18.56, 127.54; P = 0.01), compared with the placebo-group. Administration of vitamin D for 24-weeks to CS subjects had beneficial effects on symptoms of depression and several metabolic biomarkers. While this preliminary study suggests that vitamin D might have beneficial effects, its clinical efficacy in individuals with a tobacco use disorder should be further validated in future clinical trials.