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The renin-angiotensin system (RAS) plays a central role in regulating blood pressure and cardiovascular health. Angiotensin-converting enzyme (ACE) facilitates the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor that contributes to hypertension and heart failure. Conversely, ACE2 converts angiotensin II into angiotensin-(1-7), a vasodilator with protective cardiovascular effects. An imbalance between ACE and ACE2 activities has been increasingly associated with the progression of cardiovascular diseases and complications related to COVID-19. This review analyzed 100 relevant studies published up to May 2024, identified through a comprehensive literature search on PubMed and Scopus. The findings highlighted that dysregulation of the ACE/ACE2 axis exacerbates cardiovascular dysfunction. The interaction of SARS-CoV-2 with ACE2 reduces its protective function, intensifying inflammatory responses and leading to complications such as lung injury and heart failure. Additionally, genetic polymorphisms in ACE and ACE2 influence individual susceptibility and severity of COVID-19. Promising therapeutic strategies, including ACE2-based peptides and angiotensin II receptor modulators, are under investigation but require further clinical validation. Targeting the ACE/ACE2 axis could provide effective treatment options for cardiovascular disease and COVID-19-related complications, warranting further in-depth research.