Purpose: Among the various risks of cardiovascular disease, hypertension and hypercholesterolemia are the greatest risks. Renin–angiotensin–aldosterone system inhibitor medication, consisting of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, as well as statins, is used to treat hypertension and hypercholesterolemia, respectively. The effect of this medication on inflammatory reactions has been demonstrated by various studies, as well as its effect on periodontal tissue. This study aims to determine the effect of renin–angiotensin–aldosterone system inhibitor medication and statins on the periodontal status of patients at risk of cardiovascular disease. Methods: Search for studies through electronic databases using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 guidelines. Studies that met the inclusion criteria are included and assessed for risk of bias and then meta-analysed. Results: Qualitative synthesis showed inconsistent results regarding the effect of RAAS inhibitors on periodontal status. Meta-analysis between the statin group compared with other interventions such as diet found that the mean bleeding on probing index found a statistically significant difference with a mean difference of -13.4% (95% CI:[-23.08;-3.72], p = 0.007), the mean clinical attachment loss did not show any significant difference with a mean difference of -0.16 mm (95% CI: [-0.40;-0.07], p = 0.17), and mean probing depth there was a statistically significant difference between groups with a mean difference of -0.38 mm (95% CI:[-0.53;-0.23], p < 0.00001). Conclusion: The effect of renin–angiotensin–aldosterone system inhibitor medication in the form of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in hypertensive patients on periodontal status showed inconsistent results and statin medication systemically could improve periodontal status, bleeding on probing index, and probing depth in patients with hypercholesterolemia. © The Author(s) 2026.