Background: Appetite is one of the main obesity-controlling factors that can be influenced by hormones, including leptin and ghrelin. This study aimed to determine the effects of zinc supplementation on the serum levels of leptin, ghrelin, C-reactive protein (CRP), and anthropometrical indices in obese individuals with increased appetite and zinc deficiency. Methods: This study was conducted among 50 individuals with body mass index > 30 kg/m² in Shiraz, Iran in 2018. The participants were randomly allocated to the intervention that consumed one capsule containing 30 mg/day zinc (ZG) and placebo group (PG) for 3 months. Moreover, all participants were prescribed calorie-restricted diet, 500 kcal/d less than their weight maintenance requirement energy. Anthropometric indices, dietary intake, serum zinc leptin, ghrelin, and CRP were measured at the baseline and after the intervention. Results: The ccomparison of mean changes in weight (-4.56 ± 2.47, P < 0.0001), body mass index (-1.65 ± 0.85, P < 0.0001), waist circumference (-5.54 ± 4.06, P < 0.0001), hip circumference (-3.19 ±1.91, P < 0.0001), and serum zinc (15.91 ± 5.24, P < 0.0001) showed a significant difference between groups with greater reduction in the zinc group. However, waist to hip ratio, ghrelin, and CRP showed no significant differences. A significant difference was revealed between groups in terms of the mean leptin concentration changes, in favor of the increase in leptin concentration in ZG (P = 0.003). Conclusion: Based on the findings, three months of zinc supplementation improved some anthropometric and biochemical measures. Further studies are needed to confirm these results.