Previous studies have separately linked either perfluoroalkyl acid (PFAA) or heavy metal exposure with kidney dysfunction. However, the relationships of co-exposure to PFAAs and heavy metals with kidney function are still unclear. To explore the associations between exposure to PFAAs and heavy metals mixtures and kidney function in adults. We conducted a cross-sectional community-based population study in Guangzhou, China, enrolling 1312 adults from November 2018 to August 2019. We quantified 13 PFAAs in serum and 14 heavy metals in plasma. We chose estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) as outcomes of interest. Distributed lag non-linear models (DLNMs) were used to check nonlinearity of individual pollutant with kidney function. Joint associations of pollutant mixtures on kidney function were assessed by Bayesian Kernel Machine Regression (BKMR) models. We further explored modification effects of gender. Most individual PFAA and heavy metal were associated with declined kidney function in single-pollutant models. We also observed significant dose-response relationships of pollutant mixtures with reduced eGFR levels and increased odds of CKD in BKMR models. Perfluoroheptanesulfonic acid (PFHpS), arsenic (As) and strontium (Sr) were the predominant contributors among pollutant mixtures. A change in log PFHpS, As and Sr concentrations from the 25th to the 75th percentile were associated with a decrease in eGFR of −5.42 (95% confidence interval (CI): −6.86, −3.98), −2.14 (95% CI: −3.70, −0.58) and −1.87 (95% CI: −3.03, −0.72) mL/min/1.73 m2, respectively, when other pollutants were at their median values. In addition, the observed associations were more obvious in females. We provided new evidence that co-exposure to PFAAs and heavy metals mixtures was associated with reduced kidney function in adults and PFHpS, As and Sr appeared to be the major contributors. Further studies are warranted to confirm our findings and elucidate the underlying mechanisms. Display omitted •Co-exposure to PFAAs and heavy metals was associated with reduced kidney function.•PFHpS, As and Sr were the predominant contributors in the joint associations.•The joint associations were more pronounced in females.