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Introduction Oxidative stress is associated with metabolic syndrome and cardiovascular disease. Crocin, is a natural carotenoid that has anti-oxidant properties. The aim of this study was to investigate the effect of a crocin preparation extracted from saffron on a measure of serum pro-oxidant/anti-oxidant status in subjects with metabolic syndrome. Materials and methods This randomized placebo-controlled clinical trial (RCT) was carried out on 60 volunteers with metabolic syndrome. The latter was defined using the International Diabetes Federation (IDF) criteria. Participants were randomly allocated to one of two groups of 30 subjects as the intervention and control groups. The intervention group received crocin tablets for 8 weeks at a dose of 15 mg twice a day; the control group were given a placebo over the same period. Blood samples were taken before and after the intervention period. Pro-oxidant–anti-oxidant balance (PAB) assay was used to evaluate the change in serum pro-oxidant, anti-oxidant balance. Results Mean serum PAB fell by 11.7% in the intervention group ( p : 0.006), whilst there was no significant change in serum PAB in the control group ( p > 0.05). The change in mean serum PAB was statistically significant between the groups ( p = 0.014). No statistically significant differences were observed in fasting blood glucose (FBG) and blood lipid profile (including cholesterol, triglycerides, LDL and HDL) between the two groups before and after the intervention ( p > 0.05). Conclusion This study demonstrates that crocin, a derivative of saffron, at a dose of 30 mg/d can significantly reduce serum PAB in individuals with metabolic syndrome.