Periodontal studies using transcriptomics, proteomics, and metabolomics encompass the collection of mRNA transcripts, proteins, and small‐molecule chemicals in the context of periodontal health and disease. The number of studies using these approaches has significantly increased in the last decade and they have provided new insight into the pathogenesis and host‐microbe interactions that define periodontal diseases. This review provides an overview of current molecular findings using ‐omic approaches that underlie periodontal disease, including modulation of the host immune response, tissue homeostasis, and complex metabolic processes of the host and the oral microbiome. Integration of these ‐omic approaches will broaden our perspective of the molecular mechanisms involved in periodontal disease, advancing and improving the diagnosis and treatment of various stages and forms of periodontal disease.