Muscle mass may play an important role in the metabolic profile of individuals with or without excess weight. Metabolic phenotypes classify individuals as healthy or unhealthy based on certain metabolic conditions. We investigated the association between skeletal mass indices (SMI) and the metabolically unhealthy phenotype in normal-weight and overweight/obese adults. A total of 660 adults aged 20 to 59 years were assessed by a population-based cross-sectional study. Muscle mass of the limbs or appendicular lean mass (ALM) adjusted for weight (SMIweight) and BMI (SMIBMI) was used to evaluate SMI. Logistic regression was employed to estimate the association between SMIweight, SMIBMI and metabolic phenotypes of normal-weight and overweight/obese individuals. Metabolically unhealthy individuals were older in both sexes. Metabolically unhealthy men had lower SMI values and higher fat percentage than metabolically healthy men. SMIweight was inversely associated with the metabolically unhealthy phenotype, both in normal-weight men (OR 0·49, 95 % CI 0·24, 0·99, P = 0·04) and in overweight/obese men (OR 0·32, 95 % CI 0·16, 0·64, P = 0·001). SMIBMI was inversely associated with the metabolically unhealthy phenotype in overweight/obese men (OR 0·36, 95 % CI 0·18, 0·72, P = 0·004), but not in normal-weight men (OR 0·70, 95 % CI 0·34, 1·43, P = 0·33). Among women, SMI showed no significant association with the phenotypes. In conclusion, the SMI are inversely associated with the metabolically unhealthy phenotype in men, especially among overweight/obese men.