The purpose of this study was to explore the relationship between the metabolic syndrome severity Z-score and kidney function by gender. We also examined the estimated glomerular filtration rate in relation to other known risk factors. The study used was a population-based prospective longitudinal research design. A total of 4,838 participants (2,683 females and 2,155 males) included individuals aged >30 years who were undergoing a health examination from 2006 to 2014 in Pingzhen City, Taiwan. In the initial generalized estimated equation model analysis, which included the covariates of age of first visit, period between the first and current visit, and metabolic syndrome severity Z-score, the results indicated that the interaction between age and metabolic syndrome severity Z-score is significantly related to the estimated glomerular filtration rate for males ( p = .040). For females, the interaction between age and metabolic syndrome severity Z-score was not significant, but a higher metabolic syndrome severity Z-score was significantly associated with lower estimated glomerular filtration rate ( p = .001). After controlling for the confounders, unhealthy behaviors, and comorbidities, the metabolic syndrome severity Z-score was still a negative predictor of estimated glomerular filtration rate in both the male ( p = .005) and female ( p = .023) models.