Cardiovascular diseases (CVD) remain the leading cause of mortality worldwide, with chronic kidney disease (CKD) constituting a significant risk factor. Despite the crucial role of amino acids as fundamental dietary components, their impact on the comorbidities of CKD and CVD has been insufficiently studied and warrants greater research attention. Therefore, this systematic review provides a comprehensive overview of the current knowledge regarding the effects of amino acid supplementation on the comorbidities associated with CVD and CKD, as the basis for novel prevention and treatment options. The databases ‘PubMed’ and ‘Web of Science’ were used to perform a literature search on the effects of amino acid supplementation on the comorbidities associated with CVD and CKD. Data synthesis was conducted based on 60 publications, comprising 13 clinical, 43 in vivo and four in vitro studies. The risk of bias was assessed using three appropriate tools. Studies were classified based on preventive or harmful effects. Altogether, 43 publications reported preventive, and 18 described adverse effects, of which three described both preventive and adverse effects of different amino acids. Only two publications showed no effects caused by amino acids. Arginine and methionine were attributed to the highest number of preventive and adverse effects, respectively. However, a limitation of most publications is the pending translation to humans. Overall, these findings suggest that amino acid supplementation as a potentially valuable addition to treatment options for CVD and CKD patients, although further clinical studies are needed for validation of these findings. This systematic review was funded by the German Research Foundation (DFG, SFB/TRR219) and was registered in the PROSPERO database (CRD42023493924).