Metabolic syndrome (MS) is becoming globally prevalent and it is clinically important because of its association with type 2 diabetes and cardiovascular disease, and some cancers. Recently, platelet count has been linked to insulin resistance and MS in addition to being a marker of hemostasis. Also, mean platelet volume (MPV) has been known to represent platelet activity. Platelet counts and MPV are modified by various biosocial and lifestyle factors such as race, age, gender, smoking habit, alcohol consumption, and physical activity. Thus, the direction and magnitude of this association may differ by gender. In this regard, proper interpretion of platelet counts and MPV by gender could be important in the people with MS. We examined the relationship between platelet counts, MPV, and MS through gender-specific analyses for 3827 Korean adults (2169 men and 1658 women) in a health examination program. In women, platelet counts were significantly higher in subjects with MS compared to in those without MS (p < 0.001), whereas MPV was significantly lower (p = 0.001). However, no such trend was observed in men. Multiple regression analyses also showed that MS is positively associated with platelet counts and inversely associated with MPV, independently of confounding variables only in women. The results suggest that platelet counts and MPV might be a surrogate marker associated with clustered MS in women.