Background: Currently used diagnostic methods in periodontics are unable to identify disease activity and progression until significant attachment loss has happened. New diagnostic modalities and parameters are needed to monitor disease progression and detect disease activity at an early stage. Aims: To determine the features of the in vivo optical spectra characteristic of periodontitis, gingivitis and healthy gingival tissue and the potential to use these spectral signatures to differentiate periodontitis from gingivitis and healthy gingiva and determine the risk of progression from gingivitis to periodontitis. Materials and Methods: 12 cross-sectional clinical trials were conducted at 6 university based dental clinics or research centers in Canada, China, Italy and Brazil from 2007 to 2014 including 562 patients with moderate to severe chronic periodontitis. Optical spectra were obtained at the chair-side using a custom designed optical probe from 705 periodontitis, 1306 gingivitis and 1691 healthy sites in situ. A modified Beer-Lambert unmixing model was used to determine tissue oxygen saturation and relative contribution of oxygenated and deoxygenated hemoglobin components. Results: Multiple hemodynamic parameters were simultaneously derived from the optical spectra of gingival tissue including tissue oxygen saturation, oxygenated hemoglobin, deoxygenated hemoglobin and total hemoglobin indices. The tissue oxygen saturation and oxygenated hemoglobin index in periodontitis was significantly lower than gingivitis and healthy gingiva (p < 0.0001) but no significant difference in oxygenated hemoglobin between gingivitis and healthy gingiva (p > 0.05). On the other hand, deoxygenated hemoglobin in periodontitis was significantly increased compared to gingivitis and healthy gingiva (p < 0.0001 ). A classification model was established to predict the risk level of gingivitis based on the features of the optical spectra of characteristic of health gum and periodontitis. Conclusions: 1) multiple local hemodynamic profiles such as tissue oxygenation and perfusion can be simultaneously generated by optical spectroscopy to reflect subclinical gingival inflammation. 2) Decreased tissue oxygenation saturation in periodontitis and gingivitis was mainly due to increased concentration of deoxygenated hemoglobin. 3) Optical spectroscopy has the potential to diagnose periodontal disease and monitor disease progression at an early stage. More longitudinal studies are needed to validate this potential.