Abstract Aim The aim of this study was to assess the levels and diagnostic accuracy of a set of potential biomarkers of periodontal tissue metabolism in gingival crevicular fluid ( GCF ) from patients with chronic periodontitis ( CP ) and asymptomatic apical periodontitis ( AAP). Materials and Methods Thirty one GCF samples from 11 CP patients, 44 GCF samples from 38 AAP patients and 31 GCF samples from 13 healthy volunteers were obtained ( N = 106). Matrix metalloproteinases ( MMP s) ‐2 and ‐9 were determined by zymography; levels of MMP ‐8 by ELISA and IFMA and MPO by ELISA . IL ‐1, IL ‐6, TNF α , DKK ‐1, Osteonectin, Periostin, TRAP ‐5 and OPG were determined by a multiplex quantitative panel. Statistical analysis was performed using linear mixed‐effects models. Results The MMP ‐9 and MMP ‐8 were higher in CP , followed by AAP , versus healthy individuals ( p < 0.05). Pro MMP ‐2, MPO , IL ‐1, IL ‐6, PTN , TRAP ‐5 and OPG were significantly higher in CP when compared with AAP and healthy patients ( p < 0.05). The highest diagnostic accuracies were observed for Pro MMP ‐2, Pro MMP ‐9, MMP ‐8 and TRAP ‐5 ( AUC > 0.97) in CP , and for the active form of MMP ‐9 and MMP ‐8 ( AUC > 0.90) in AAP . Conclusion Gingival crevicular fluid composition is modified by CP and AAP . MMP ‐9 and MMP ‐8 show diagnostic potential for CP and AAP , whereas MMP ‐2 and TRAP ‐5 are useful only for CP .