Background: Immunocompromised individuals are at heightened risk for oral diseases, which can exacerbate systemic conditions, creating a bidirectional relationship. Understanding these associations is essential for optimizing healthcare strategies. Aim: This systematic review explores the correlation between immunocompromised diseases and oral health, highlighting common oral manifestations, systemic implications, and the effectiveness of interventions. Methods: A comprehensive literature search was conducted in PubMed, MEDLINE, Embase, Web of Science, and Cochrane Library for studies published up to September 2023. Studies on immunocompromised conditions, including HIV/AIDS, diabetes mellitus, cancer, autoimmune diseases, and organ transplantation, were included. Data were synthesized narratively and statistically where possible. Results: Among 38 studies reviewed, oral candidiasis, mucositis, and periodontitis were the most prevalent conditions, affecting 35-80% of immunocompromised individuals. Periodontitis was strongly associated with systemic inflammation, contributing to cardiovascular diseases and poor glycemic control. Interventions, such as antiretroviral therapy and non-surgical periodontal therapy, reduced disease prevalence and improved systemic outcomes. Geographic disparities highlighted the need for equitable healthcare access. Conclusion: Immunocompromised states significantly impact oral health, which, in turn, affects systemic conditions. Integrated healthcare approaches are critical to improving outcomes in these populations.