Exercise and dietary interventions have been described to positively affect metabolic syndrome (MetS) via molecular induced changes. The purpose of this study was to investigate the effects of dietary carbohydrate restriction and aerobic exercise on Retinol Binding Protein 4 (RBP4) and Fatty Acid Binding Protein 5 (FABP5) in middle-aged men with metabolic syndrome. The study had a randomized, double-blinded, parallel controlled design. Forty middle-aged men with metabolic syndrome (age: 53.97 ± 2.85 years, body mass index = 31.09 ± 1.04 kg/m2) were randomly assigned to four groups, aerobic exercise (AE; n=10), Ketogenic diet (KD; n=10), AE combined with KD (AE+KD; n=10) or control (C; n=10). RBP4, FABP5, body composition [body mass, body mass index and body fat], insulin resistance, insulin sensitivity, and MetS factors were evaluated prior to and after the 12-weeks intervention. AE+KD significantly decreased the body fat percentage (p = 0.006), body mass index (p = 0.001), Zmets (p = 0.017), RBP4 (p = 0.017) and the homeostasis model of insulin resistance (HOMA-IR) (p = 0.001) as compared to control group and marginally significantly decreased the Zmets as compared to exercise group (p = 0.086). KD significantly decreased RBP4 levels as compared to control group (p = 0.041). Only the AE intervention (p = 0.045) significantly decreased FABP5 levels. Combining intervention of carbohydrate restriction with AE compared with carbohydrate restriction and AE alone, improved RBP4, HOMA-IR as well as different body composition and MetS factors in middle-aged men with metabolic syndrome.