<p>Muscle mass and strength influence various age-related health outcomes, however their individual and joint associations with biological aging remain understudied. This study investigated the associations of muscle health with epigenetic aging based on DNA methylation in blood samples, among middle-aged and older adults. We analyzed data from 1,121 individuals from the 1999–2002 cycles of the National Health and Nutrition Examination Survey. Muscle mass was assessed using the appendicular skeletal muscle mass index, with low muscle mass defined as &lt; 7.0&#xa0;kg/m² in males and &lt; 5.5&#xa0;kg/m² in females. Muscle strength was evaluated using isokinetic knee extensor force, and categorized into high or low strength based on the sample sex-specific median. Three epigenetic age acceleration measures—PhenoAA, Grim2AA and DunedinPoAm—were examined using multivariable linear regression models. Individual and joint associations were assessed, with analyses stratified by race/ethnicity and sex. Compared to individuals with lower muscle mass, those with higher mass had lower EAA (β: -1.25 for Grim2AA; β: -3.01 for DunedinPoAm; <i>P</i> &lt; 0.01). Similarly, participants with higher muscle strength showed lower EAA compared to those with lower strength (β: -1.66 to -1.01, <i>P</i> &lt; 0.01). Associations were more pronounced in males but not in non-Hispanic Whites. Individuals with better muscle health (higher muscle mass and strength) had lower EAA compared to those with poorer muscle health, across all EAA measures (β: -4.07 to -1.56, <i>P</i> &lt; 0.05). Greater muscle mass and strength were associated with slower biological aging, suggesting the potential importance of maintaining muscle health in promoting healthy aging.</p>