Periodontitis (PD) is a chronic inflammatory disease of the periodontium characterized by the formation of gingival pockets and gingival recession. The local inflammatory environment can lead to the destruction of the extracellular matrix and subsequent bone loss. The pathophysiology of PD involves interactions between genetic predisposition, lifestyle, environmental factors, the oral microbiota condition, systemic health disorders, innate and adaptive immune responses, and various host defenses. The review highlighted the importance of the oral cavity condition in systemic health. Thus, a correlation between harmful oral microbiota and cardiovascular disease (CVD)/diabetes/ arthritis, etc, progressions through inflammation and bacterial translocation was highlighted. Antecedents increase an individual's risk of developing PD, trigger initiate microbe-host immunologic responses, and mediators sustain inflammatory interactions. Generally, this review explores the antecedents, triggers, and mediators along the pathophysiological continuum of PD. An analysis of modern approaches to treating periodontitis, including antibiotics for systemic and local use, was carried out. The potential role of natural ingredients such as herbal extracts, phytoconstituents, propolis, and probiotics in preventing and treating PD was highlighted.