Currently, it is unclear whether creatine phosphokinase (CPK) affects bone mineral density (BMD) in adolescents. We sought to clarify the relationship between CPK and total BMD in adolescents aged 12 to 19 years within normal values by conducting this study. A cross-sectional study was conducted using the 2011 to 2018 National Health and Nutrition Survey data to examine 1188 males (average age, 15.2 years) and 1629 females (average age, 15.4 years). In this study, CPK was the independent variable and total BMD was the outcome variable. In addition to using multivariate linear regression models, subgroup analyses were also conducted in order to examine the relationship between CPK levels and total BMD within normal ranges. Significant positive association was observed between the CPK levels and total BMD in adolescents (model 1: 0.0003 [0.0002, 0.0004], model 2: 0.0004 [0.0003, 0.0005] and model 3: 0.0004 [0.0003, 0.0004]). After adjusting for age, gender, race/ethnicity, body mass index, dietary protein intake, dietary protein intake, dietary fiber intake, poverty to income ratio, physical activities, total cholesterol, total protein, blood urea nitrogen, phosphorus, and serum calcium, CPK levels remained significantly associated with BMD (regression coefficients for quartiles 2 to 4 vs quartile1 were 0.0002, 0.0072, and 0.0154, respectively; P for trend <.001). The association was positive even when stratified by age, gender, and race. Further, adolescents aged 16 to 19 years were more likely to report positive relationships than adolescents aged 12 to 15 years. And the phase relationship between total BMD and CPK was further enhanced in boys. The results of our study show that CPK levels within the normal range are positively associated with total BMD in adolescents aged 12 to 19 years. Additionally, CPK may be a potential biomarker of bone health among adolescents.