Background: The improved physical action following administration of supplements to bodybuilders was supported by changes in laboratory parameters. Despite the fact that these supplements are sometimes associated both advantage and side effects, this study were conducted for the purpose of evaluating the possible effects of some commonly used supplements in bodybuilders on the hematological and biochemical parameters. Materials and Methods: In this study, we included 40 male bodybuilders as cases and 40 controls in the age group of 20-40 years. They used different kinds of supplements for 1 year. In general, all the supplements used were classified into two groups: hormonal and non-hormonal. Laboratory tests were requested for evaluation of hematological and biochemical parameters. Results: In an equation model, we found that weight (P = 0.024), duration of bodybuilding (P < 0.001), and duration of hormone supplement consumption (P < 0.001) were loaded significantly on the latent variables, demographic and dietary supplement, respectively. The relationship between dietary supplement and biochemical and hematological parameters was significant (P = 0.01) and some of these parameters including creatinine (P = 0.023), blood aspartate aminotransferase (AST) (P < 0.001), alanine aminotransferase (ALT) (P < 0.001), and red blood cell distribution (RDW) (P = 0.046) had a significant role than others. In a multivariate regression model, we found that WBC (P < 0.001), platelets (P < 0.001), blood urea nitrogen (BUN; P < 0.001), creatinine (P < 0.001), AST (P = 0.005), and ALT (P = 0.001) were higher in athletes than in controls. Conclusions: It is strongly advised that there should be some concerns about possible supplement-induced changes in the laboratory exams for bodybuilders. The available supplements are unchecked and not approved by the US Food and Drug Administration (FDA). More studies should be designed for a better and precise administration of each supplement in athletes.