Current conventional thrombolytic drugs have some limitations, including a short half-life, several adverse effects, low fibrin specificity, and high cost. Therefore, new thrombolytic sources have been widely investigated worldwide. In this sense, this work aims to evaluate the state of the art of the thrombolytic potential of different bioactive compounds produced from microalgae and cyanobacteria. Then, a systematic literature search was conducted using ScienceDirect, Medline (PubMed), Springer Link, Wiley Online Library, Scielo, MDPI, and BVS electronic databases to select original studies about thrombolytic agents obtained from microalgae and cyanobacteria. After the selection process, 20 studies met the inclusion criteria and were included in the final analysis. Most studies showed promising thrombolytic activity of polysaccharides or proteins produced by cyanobacteria and obtained through homogenization methods. Moreover, the majority of the studies used methods such as activated partial thromboplastin time, prothrombin time, thrombin time, or platelet aggregation tests as parameters to determine the thrombolytic activity. In conclusion, various bioactive compounds from microalgae and cyanobacteria showed high potential to act as alternative thrombolytic therapy, but some characteristics such as mechanism of action, cytotoxicity, immunogenicity and stability parameters need to be more exploited to make the application of these agents feasible in the future.