Periodontitis is a complex immune‐inflammatory disease that results from a preestablished infection in gingiva, mainly due to Gram‐negative bacteria that colonize deeper in gingival sulcus and latter periodontal pocket. Host inflammatory and immune responses have both protective and destructive roles. Although cytokines, prostaglandins, and proteases struggle against microbial burden, these molecules promote connective tissue loss and alveolar bone resorption, leading to several histopathological changes, namely destruction of periodontal ligament, deepening of periodontal pocket, and bone loss, which can converge to attain tooth loss. Despite the efforts of genomics, transcriptomics, proteomics/peptidomics, and metabolomics, there is no available biomarker for periodontitis diagnosis, prognosis, and treatment evaluation, which could assist on the established clinical evaluation. Nevertheless, some genes, transcripts, proteins and metabolites have already shown a different expression in healthy subjects and in patients. Though, so far, ‘omics approaches only disclosed the host inflammatory response as a consequence of microbial invasion in periodontitis and the diagnosis in periodontitis still relies on clinical parameters, thus a molecular tool for assessing periodontitis lacks in current dental medicine paradigm. Saliva and gingival crevicular fluid have been attracting researchers due to their diagnostic potential, ease, and noninvasive nature of collection. Each one of these fluids has some advantages and disadvantages that are discussed in this review.