Background: Physical activity is indispensable in the management of chronic kidney disease (CKD). The aim of this study was to investigate gender difference in the association of physical activity with mortality among the CKD population. Methods: In total, 3701 participants with CKD from the 2011 to 2018 NHANES with linked mortality data were classified into different groups based on the intensity of self-reported physical activity. Multivariable-adjusted Cox proportional hazards models were used to examine the associations between physical activity and mortality. Results: During the median follow-up of 53.7 months, 694 all-cause deaths and 226 cardiovascular deaths were recorded. Patients were categorized into extremely highly active (>1500 MET-min/week), highly active (>600, <= 1500 MET-min/week), low-active (>0, <= 600 MET-min/week), or inactive (0 MET-min/week) groups. Among males, the multivariable Cox regression showed that the low-active group (HR, 0.67; 95% CI, 0.48-0.93) and highly active group (HR, 0.60; 95% CI, 0.41-0.88) were independently associated with lower risks for all-cause mortality, compared to the inactive group. The risks of all-cause mortality did not further decrease once physical activity surpassed 1500 MET-min/week, indicating a U-shaped association in males. In females, only the extremely highly active group (>1500 MET-min/week) was significantly associated with a mortality risk compared to inactivity (HR, 0.59; 95% CI, 0.39-0.89). Conclusions: Any amount of physical activity is associated with reduced all-cause mortality in male CKD participants, while in female patients, only the extremely highly active group shows the significant association.